MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Combinatorial Chemistry and High Throughput Screening' source. Thu, 09 Feb 2012 13:01:34 +0100 http://www.medworm.com/index.php?rid=5654093&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22292777%26dopt%3DAbstract In this study, we focus on the DNA template, the subject of PCR experiment, and introduce a support vector machine (SVM) based method to help evaluate PCR result. Through the Jackknife cross-validation test, our method achieves an accuracy of 92.06%, with 93.62% sensitivity and 90.53% specificity. PMID: 22292777 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654093 Tue, 31 Jan 2012 05:00:00 +0100 5654093 http://www.medworm.com/index.php?rid=5654092&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22292778%26dopt%3DAbstract Authors: Piltan M, Moradi L, Salimi H, Zargoosh K, Zarei SA Abstract Poly(ethylene glycol) (PEG) has been used as a sustainable, non-volatile, and environmentally friendly reaction solvent for synthesis of functionalized anilines and benzenes via the reaction of malononitrile and β-ketoester derivatives in the presence of activated acetylenesat 80o C. No additional solvent and catalyst are required. PMID: 22292778 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654092 Mon, 30 Jan 2012 05:00:00 +0100 5654092 http://www.medworm.com/index.php?rid=5654096&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22272661%26dopt%3DAbstract Authors: Mezler M, Hermann D, Swensen AM, Draguhn A, Terstappen GC, Gross G, Schoemaker H, Freiberg G, Pratt S, Gopalakrishnan SM, Nimmrich V Abstract Dysfunction of P/Q-type calcium channels is thought to underlie a variety of neurological diseases. There is evidence that migraine, Alzheimer´s disease, and epilepsy involve a gain-of-function of the channel, leading to abnormal presynaptic vesicle release. P/Q-channel blockers may normalize current flow and consequently lead to an alleviation of disease symptoms. Although the medical need is high, there are no such compounds on the market. Here we describe a high-throughput screen for P/Q-type calcium channel blockers and the confirmation of hits by automated electrophysiology. We generated a HEK293 cell line stably expressing the... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654096 Tue, 24 Jan 2012 05:00:00 +0100 5654096 http://www.medworm.com/index.php?rid=5654095&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22272662%26dopt%3DAbstract Authors: Dubrovskiy AV, Markina NA, Larock RC Abstract The iodocyclization of functionally-substituted alkynes provides an excellent way to prepare a wide range of iodoheterocycles, which can then be readily elaborated through palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, Hartwig-Buchwald, and carbonylation processes into libraries of medicinally relevant heterocycles. The synthesis of libraries of indoles, benzofurans, benzothiophenes, isocoumarins and pyrones, cyclic imidates, isoxazoles, furans using this approach is reviewed. This technology is very versatile, proceeds under mild reaction conditions in high yields, and tolerates considerable functionality. PMID: 22272662 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screen... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654095 Tue, 24 Jan 2012 05:00:00 +0100 5654095 http://www.medworm.com/index.php?rid=5654094&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22272691%26dopt%3DAbstract Authors: El Maatougui A, Azuaje J, Coelho A, Cano E, Yañez M, López MC, Yaziji V, Carbajales C, Sotelo E Abstract We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane- 4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structureactivity relationships in this series as well as to identify novel derivatives that are up to 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone. PMID: 22272691 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654094 Mon, 23 Jan 2012 05:00:00 +0100 5654094 http://www.medworm.com/index.php?rid=5654146&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263857%26dopt%3DAbstract Authors: Charati FR, Hossaini Z, Moradian M, Jafari A, Yazdani A Abstract A one-pot synthesis of cyclopentanone derivatives from phosphorus ylide under lab-type microwave assisted methodology was described. The phosphorus ylides were obtained via the reaction of activated acetylenic compounds, ethyl 4-chloroacetoacetate and triphenylphosphine. The structure of phosphorus ylides was assigned by 1H, 13C and 31P-NMR. The phosphorus ylides as precursor were crystallized as two enantiomers (R,R) and (S,S) and the structure of was confirmed by single X-ray crystallography. PMID: 22263857 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654146 Thu, 19 Jan 2012 05:00:00 +0100 5654146 http://www.medworm.com/index.php?rid=5654116&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263858%26dopt%3DAbstract Authors: Wang Y, Ding Y, Wen H, Lin Y, Hu Y, Zhang Y, Xia Q, Lin Z Abstract Drug resistance to existing antibiotics poses alarming threats to global public health, which inspires heightened interests in searching for new antibiotics, including antimicrobial peptides (AMPs). Accurate prediction of antibacterial activities of AMPs may expedite novel AMP design and reduce the costs and efforts involved in laboratory screening. In the present study, a novel quantitative prediction method of AMP was established by quantitative structure-activity relationship (QSAR) modeling based on the physicochemical properties of amino acids. The indices of these physicochemical properties were used to define AMP. The structural variables were optimized by stepwise regression (STR). Three series of A... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654116 Thu, 19 Jan 2012 05:00:00 +0100 5654116 http://www.medworm.com/index.php?rid=5654115&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263859%26dopt%3DAbstract Authors: Wang K, Hu X, Wang Z, Yan A Abstract Acetylcholinesterase has long been considered as a target for Alzheimer disease therapy. In this work, several classification models were built for the purpose of distinguishing acetylcholinesterase inhibitors (AChEIs) and decoys. Each molecule was initially represented by 211 ADRIANA.Code and 334 MOE descriptors. Correlation analysis, F-score and attribute selection methods in Weka were used to find the best reduced set of descriptors, respectively. Additionally, models were built using a Support Vector Machine and evaluated by 5-, 10-fold and leave-one-out cross-validation. The best model gave a Matthews Correlation Coefficient (MCC) of 0.99 and a prediction accuracy (Q) of 99.66% for the test set. The best model also gave good result... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654115 Thu, 19 Jan 2012 05:00:00 +0100 5654115 http://www.medworm.com/index.php?rid=5654114&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263860%26dopt%3DAbstract In this study, quantitative structure-activity relationship (QSAR) analyses for 190 narlaprevir derivatives were conducted using comparative molecular field analysis (CoMFA), comparative molecular indices analysis (CoMSIA) and hologram quantitative structure-activity relationship (HQSAR) techniques. Both of the best CoMFA and HQSAR models showed statistical significance for the training set and good predictive accuracy for the test set, which strongly manifested the robustness of the CoMFA and HQSAR models. The CoMFA contour maps and the HQSAR contribution maps were both presented. Furthermore, based on the essential factors for ligand binding derived from the QSAR models, sixteen new derivatives were designed and some of them showed higher inhibitory activities confirmed by our models and... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654114 Thu, 19 Jan 2012 05:00:00 +0100 5654114 http://www.medworm.com/index.php?rid=5654113&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263861%26dopt%3DAbstract Authors: Siyad MA, Kumar GS Abstract Here we present a novel beaded chemically stable, highly permeable hydrophobic/hydrophilic balanced support for solid phase peptide synthesis. The resin (SPED) was prepared by free radical suspension polymerization using monomers styrene and 9-decen-1-ol with amphiphilic cross-linking agent polyethyleneglycol diacrylate (Mn≈ 258). Different cross-linking densities were prepared to check the extent of swelling in different polar and non-polar solvents. The SPED resin was characterized with IR, 13C NMR and surface by SEM. The chemical stability of the support in various peptide synthetic conditions was investigated and monitored by IR spectroscopy. To evaluate the applicability of the new resin in synthetic conditions more challenging peptide se... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654113 Thu, 19 Jan 2012 05:00:00 +0100 5654113 http://www.medworm.com/index.php?rid=5654105&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263862%26dopt%3DAbstract Authors: Yardım Y, Levent A, Ekin S, Keskin E, Oto G, Sentürk Z Abstract A number of polycyclic aromatic hydrocarbons (PAHs) have been shown to be toxicants, and induce carcinogenic and immunotoxic effects. As a model PAH agent, 7,12-dimethylbenz[a]anthracene (DMBA) was the strongest one tested in terms of its biological activities and biotransformation. A new and simple high-performance liquid chromatographic (HPLC) method with diode-array detection at 290 nm was developed and validated for monitoring of DMBA in different matrices (serum, liver and kidney) of rats orally treated with DMBA. Furthermore, the applicability of adsorptive transfer stripping voltammetry (AdTSV) on the pencil-lead graphite electrode to these samples was illustrated using our previously reported data fo... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654105 Thu, 19 Jan 2012 05:00:00 +0100 5654105 http://www.medworm.com/index.php?rid=5654103&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263863%26dopt%3DAbstract Authors: Hossaini Z, Rostami-Charati F, Firoziyan S, Sabbaghan M, Khalilzadeh MA Abstract An efficient synthesis of dialkyl pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates, pyrrolo[1,2-a]quinoline-1,2-dicarboxylates and indolizines is described via one-pot reactions of isoquinoline, quinoline or pyridine and phenacyl bromids with dialkyl acetylenedicarboxylates or diaryloylacetylene under solvent-free conditions at 50 oC. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods. PMID: 22263863 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654103 Thu, 19 Jan 2012 05:00:00 +0100 5654103 http://www.medworm.com/index.php?rid=5654102&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263864%26dopt%3DAbstract Authors: Cerón MA, Guzmán-Lucero DJ, Palomeque JF, Martínez-Palou R Abstract Seventy-five ionic liquids were efficiently synthesized in parallel format under one-pot, solvent-free microwave-assisted synthesis. These compounds were evaluated as extracting agents of nitrogen-containing compounds from a real Diesel feed before being submitted to hydrodesulfurization process to obtain ultralow sulfur Diesel. Our results showed that halogenated ionic liquids are an excellent alternative due to these compounds are cheaper, present high selectivity for the extraction of nitrogen-containing compounds and can be regenerated and recycled. PMID: 22263864 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654102 Thu, 19 Jan 2012 05:00:00 +0100 5654102 http://www.medworm.com/index.php?rid=5654101&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263865%26dopt%3DAbstract Authors: Abdolmohammadi S, Balalaie S Abstract A simple one-pot method for the preparation of 7-amino-2,4-dioxo-5-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitriles 4 from aromatic aldehydes, malononitrile and 4(6)-aminouracil in the presence of ZrO2 nanoparticles (ZrO2 NPs) as an efficient heterogeneous catalyst is described. The procedure has the advantages of high yields (86-97%), short reaction time (2h) and an environmentally friendly specificity. PMID: 22263865 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654101 Thu, 19 Jan 2012 05:00:00 +0100 5654101 http://www.medworm.com/index.php?rid=5654100&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263889%26dopt%3DAbstract Authors: Al-Othman ZA, Ali I, Asim M, Khan TA Abstract Polysaccharide CSPs are recognized widely in chiral chromatography but the introduction of immobilized phases (Chiralpak IA, Chiralpak IB and Chiralpak IC columns) is a remarkable achievement. The immobilized CSPs can be used with organic, normal and reversed phase modes; even with prohibited solvents too (tetrahydrofuran, chlorofom, dichloromethane, acetone, 1,4-dioxane, ethylacetate, and certain other ethers). Their susceptibilities to work with a wide range of solvents have increased the range of applications including chiral recognition mechanisms. Besides, these are also useful for monitoring the progress of stereo-specific reactions; normally need prohibited solvents. The present review describes the various aspects of co... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654100 Thu, 19 Jan 2012 05:00:00 +0100 5654100 http://www.medworm.com/index.php?rid=5654099&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263890%26dopt%3DAbstract Authors: Wang SL, Zhang G, Jie D, Jiang B, Wang XH, Tu SJ Abstract A new multicomponent domino reaction for rapid and regioselective synthesis of highly functionalized benzo[h]naphtho[2,3-a]acridine-15,16(5H,14H)-diones has been established. The reaction can be conducted by using readily available and inexpensive substrates under microwave irradiation. The procedures are facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors as well as protection/deprotection of functional groups. This method is much more efficient due to short reaction times and easy work up. The resulting naphthoacridines have been readily converted into benzoquinoxaline-fused benzoquinoline analogues by treating with benzene-1,2-diamine under microwave irradiation. ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654099 Thu, 19 Jan 2012 05:00:00 +0100 5654099 http://www.medworm.com/index.php?rid=5654098&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263891%26dopt%3DAbstract Authors: Tseng CC, Tasi CH, Sun CM Abstract A novel protocol for rapid assemble of benzimidazole framework has been demonstrated. This method incorporated with light fluorous-tag provides a convenient method for diversification of benzimidazoles and for easy purification via fluorous solid-phase extraction (F-SPE) in a parallel manner. The key transformation of this study involves in situ reduction of aromatic nitro compound, amide formation, cyclization and aromatization promoted by microwave irradiation in a one-pot fashion. The strategy is envisaged to be applied for establishment of drug-like small molecule libraries for high throughput screening. PMID: 22263891 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654098 Thu, 19 Jan 2012 05:00:00 +0100 5654098 http://www.medworm.com/index.php?rid=5654097&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22263892%26dopt%3DAbstract Authors: Charati FR, Hossaini Z, Khalilzadeh MA Abstract Three-component reaction of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone, dialkyl acetylenedicarboxylates and isocyanides in water are described as efficient and green synthetic procedure for preparation of 9H-furo[2,3-f]chromene-8,9-dicarboxylates in excellent yield. In these reactions, 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone was extracted from rhizomes of Petasites hybridus from northern Iran. The structure of this compound was determined by 1H, 13C-NMR and IR spectroscopy and confirmed by X-ray diffraction analysis. This procedure provides rapid access to novel and diversely substituted 9H-furo[2,3-f]chromene-8,9-dicarboxylate derivatives. PMID: 22263892 [PubMed - as supplied by publisher] (Sou... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5654097 Thu, 19 Jan 2012 05:00:00 +0100 5654097 http://www.medworm.com/index.php?rid=5618247&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22256970%26dopt%3DAbstract Authors: Ibáñez G, Shum D, Blum G, Bhinder B, Radu C, Antczak C, Luo M, Djaballah H Abstract Protein methyltransferases (PMTs) orchestrate epigenetic modifications through post-translational methylation of various protein substrates including histones. Since dysregulation of this process is widely implicated in many cancers, it is of pertinent interest to screen inhibitors of PMTs, as they offer novel target-based opportunities to discover small molecules with potential chemotherapeutic use. We have thus developed an enzymatic screening strategy, which can be adapted to scintillation proximity imaging assay (SPIA) format, to identify these inhibitors. We took advantage of S-adenosyl-L-[3H-methyl]-methionine availability and monitored the enzymatically catalyzed [3H]-methyl additi... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5618247 Tue, 17 Jan 2012 05:00:00 +0100 5618247 http://www.medworm.com/index.php?rid=5575603&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221052%26dopt%3DAbstract Authors: Huang C PMID: 22221052 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575603 Wed, 04 Jan 2012 05:00:00 +0100 5575603 http://www.medworm.com/index.php?rid=5575602&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221053%26dopt%3DAbstract Authors: Zhou S, Yi T, Zhang B, Huang F, Huang H, Tang J, Zhao X Abstract Advances in novel tumor-associated antigen (TAA) screening strategy have accelerated the identification and characterization of biomarkers and potential target molecules for tumor subtyping, diagnosis and therapeutics, which may facilitate early detection and diagnosis of the diseases individually and enhance treatment approaches for cancer. Over the past decades, a plethora of non-invasive methodologies dedicated to identify novel target molecules have been primarily focusing on the discovery of human tumor antigens recognized by the autologous antibody repertoire or cytotoxic T lymphocytes, among which serological analysis of recombinant cDNA expression libraries (SEREX) technology is chronologically first ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575602 Wed, 04 Jan 2012 05:00:00 +0100 5575602 http://www.medworm.com/index.php?rid=5575601&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221054%26dopt%3DAbstract Authors: Nai HS, Lau QC Abstract DNA hypermethylation of CpG islands plays an important role in gene regulation during cancer development. Many techniques have been developed to detect global DNA methylation in cancer cells compared to normal tissues. This knowledge helps us to better understand cancer progression and also aids in the development of new biomarker for early cancer detection. New prognostic tools for monitoring drug efficacy during cancer treatment can also be developed. In this review, we will examine the different techniques that have been used to study DNA methylation, as well as the emerging high resolution, high throughput techniques for identification of methylated regions to defining cancer related genes in the cancer methylome. PMID: 22221054 [PubMed - as... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575601 Wed, 04 Jan 2012 05:00:00 +0100 5575601 http://www.medworm.com/index.php?rid=5575600&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221055%26dopt%3DAbstract Authors: Liang S, Xu Z, Xu X, Zhao X, Huang C, Wei Y Abstract The mass spectrometry (MS)-based quantitative proteomics is powerful to discover disease biomarkers that can provide diagnostic, prognostic and therapeutic targets, and it also can address important problems in clinical and translational medical research. The current status of MS-based quantification strategy and technical advances of several main quantitative assays (two-dimensional (2-D) gel-based methods，stable isotope labeling with amino acids in cell culture (SILAC), isotope-coded affinity tag (ICAT), the isobaric tags for relative and absolute quantification (iTRAQ),18O labeling，absolute quantitation and label-free quantitation) have been summarized and reviewed. At present, except 2-D gel-based methods, severa... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575600 Wed, 04 Jan 2012 05:00:00 +0100 5575600 http://www.medworm.com/index.php?rid=5575599&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221056%26dopt%3DAbstract Authors: Wang D, Li Y, Zhang Y, Liu Y, Shi G Abstract G protein-coupled receptors (GPCRs)，which constitute one of the largest and most versatile families of cell surface receptors，are involved in a wide spectrum of physiological functions, such as, neuronal transmission, chemotaxis, pacemaker activity and embryonic development. Therefore, in the past a few years，GPCR families have become very important targets in pharmaceutical design. However, according to the human genome project, there are approximately 1000 genes encoding GPCRs, only about 200 of GPCRs have known ligands and functions. Searching for ligands of the unknown GPCRs and better modulators of known GPCRs are currently attracting lots of interest. High throughput screening (HTS), which is commonly defined as an ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575599 Wed, 04 Jan 2012 05:00:00 +0100 5575599 http://www.medworm.com/index.php?rid=5575598&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221057%26dopt%3DAbstract Authors: Mo C, Zhang W, Liu L, Wang L, Xiao H Abstract Aging and its related diseases are severe issues in modern society. Many efforts have been made to understand the mechanisms of aging and find the ways for preventing age-related diseases. Identifying the compounds targeting aging-related signals is a challenging work because there are so many proteins and signals involved. Recently, companying with the progresses in high throughput screening (HTS) technology, more and more small molecules targeting aging-related pathologic processes have been identified. In this review, we introduce the basic workflow, classification and assay strategies of HTS technology, and sort out known small molecules identified via HTS technology by their roles in aging related diseases, such neural deg... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575598 Wed, 04 Jan 2012 05:00:00 +0100 5575598 http://www.medworm.com/index.php?rid=5575597&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221058%26dopt%3DAbstract Authors: Xie N, Huang C, Lei Y, Ran Y, Huang C Abstract Lipid rafts are sphingolipid- and cholesterol-enriched membrane microdomains, which are involved in entry, assembly and budding of various types of viruses. Identification of rafts associated proteins modified by virus infection could therefore provide novel insights into the mechanisms of virus infection as well as the development of new biomarkers for diagnosis and drug development. Proteomic approaches, such as LC-ESI-MS/MS, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), two-dimensional difference gel electrophoresis (2D-DIGE), isotope-coded affinity tags (ICAT), Proteolytic18O Labeling, isotope Tags for Relative and Absolute Quantification (iTRAQ), Stable Isotope Labeling with Amino acids in Cell culture (SI... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575597 Wed, 04 Jan 2012 05:00:00 +0100 5575597 http://www.medworm.com/index.php?rid=5575596&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221059%26dopt%3DAbstract Authors: Bu Q, Huang Y, Yan G, Cen X, Zhao YL Abstract The repertoire of small-molecular-weight substances present in cells, tissue and body fluids are known as the metabolites. The global analysis of metabolites, such as by high-resolution 1H nuclear magnetic resonance spectroscopy and mass spectrometry, is integral to the rapidly expanding field of metabolomics, which is making progress in various diseases. In the area of cancer and metabolic phenotype, the integrated analysis of metabolites may provide a powerful platform for detecting changes related to cancer diagnosis and discovering novel biomarkers. In this review, metabolomics including the technologies in metabolomics research and extracting information from metabolomics datasets are described. Then we discuss the challen... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575596 Wed, 04 Jan 2012 05:00:00 +0100 5575596 http://www.medworm.com/index.php?rid=5575595&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221060%26dopt%3DAbstract Authors: Zeng J, Xie K, Wu H, Zhang B, Huang C Abstract Tumorigenesis may be affected by various cellular components in the tumor cells and/or by tumor microenvironmental factors. Cytokines, including chemokines (chemotactic cytokines) are polypeptides or small soluble proteins generated by leukocytes and non-leukocytes, including cancer cells and stromal cells, for example, fibroblasts, mesenchymal stem cells (MSCs) and epithelial cells. Cytokines exert their functions on the cells that secrete them, on nearby cells, or on distant cells. Chemokines have expanded beyond their initial roles in impinging on every aspect of the immune system and leukocyte biology. They display multifunctional effects for regulating angiogenesis, tumor cell proliferation and apoptosis, mediating tumor ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575595 Wed, 04 Jan 2012 05:00:00 +0100 5575595 http://www.medworm.com/index.php?rid=5575594&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221061%26dopt%3DAbstract Authors: Zhang H, Hu H, Deng C, Chun Y, Zhou S, Huang F, Zhou Q Abstract Biomarkers are currently widely used to diagnose diseases, monitor treatments, and evaluate potential drug candidates. Research of differential Omics accelerate the advancements of biomarkers' discovery. By extracting biological knowledge from the 'omics' through integration, integrative system biology creates predictive models of cells, organs, biochemical processes and complete organisms, in addition to identifying human disease biomarkers. Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. Several integrative system biology approaches ha... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575594 Wed, 04 Jan 2012 05:00:00 +0100 5575594 http://www.medworm.com/index.php?rid=5575593&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221062%26dopt%3DAbstract Authors: Ou L, Duan D, Wu J, Nice E, Huang C Abstract Recent advances in high-throughput screening technologies have accelerated the identification and characterization of potential factors involved in host-virus interactions, facilitating early detection and diagnosis of diseases, as well as providing promising drug targets. The last decade has seen a plethora of successful examples of high-throughput screening approaches, especially siRNA screening. With support from protein interaction studies, mRNA expression profiling, and bioinformatics, siRNA screening has also been successfully utilized to identify host factors required for a number of viruses including HIV, West Nile virus and H1N1 virus. Such studies have raised the awareness of virologists, and have opened a new chapter ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575593 Wed, 04 Jan 2012 05:00:00 +0100 5575593 http://www.medworm.com/index.php?rid=5575592&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221063%26dopt%3DAbstract Authors: Zhou M, Luo H, Li Z, Wu F, Huang C, Ding Z, Li R Abstract It has been a very long history for human to resist diseases. During this period, a large number of drugs that could kill or inhibit the growth of microbe has been discovered, most of which were natural products. However, there may still be a large amount of antimicrobial medicines in natural compounds which have not been found yet. The ways of screening for antimicrobial always cost a long time and need a lot of manpower before. However, in recent years, a lot of new antimicrobial targets, antimicrobial drugs and screening methods which are simpler, faster and more efficient have been invented. In this paper the newly discovered targets, natural products and representative technologies were reviewed, which were exp... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575592 Wed, 04 Jan 2012 05:00:00 +0100 5575592 http://www.medworm.com/index.php?rid=5575591&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221064%26dopt%3DAbstract Authors: Lei Y, Xie K, Huang K, Wu H, Huang C Abstract Ubiquitylation is a reversible post-translational modification pathway that regulates a variety of cellular processes including protein degradation and trafficking, intracellular localization, DNA repair, immune response and cell-cycle progression. Deubiquitylating enzymes (DUBs) can remove the ubiquitin from the modified proteins and reverse the ubiquitylation-induced biological processes; hence it isn't hard to understand that viral pathogens take advantage of the host cell ubiquitin system through disturbing DUBs, for infection and replication. Although accumulated virus-related DUBs have been defined, but how viruses regulate their expression and activities is poor understand because of limitation of technologies. Recently,... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575591 Wed, 04 Jan 2012 05:00:00 +0100 5575591 http://www.medworm.com/index.php?rid=5575590&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221065%26dopt%3DAbstract Authors: Xiang M, Cao Y, Fan W, Chen L, Mo Y Abstract Over the past decade, there have been remarkable advances in the area of computer-aided drug design (CADD), which has been applied at almost all stages in the drug discovery pipeline. The generation of initial lead compounds and the subsequent optimization aimed at improving potency and pharmacological properties are the core activities among all. The development in these aspects over the past years will be the focus of this review. PMID: 22221065 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5575590 Wed, 04 Jan 2012 05:00:00 +0100 5575590 http://www.medworm.com/index.php?rid=5341076&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999654%26dopt%3DAbstract Authors: Feng C, Wang Q, Lu C, Yang G, Chen Z Abstract Polyethylene glycol is found to be a nontoxic and recyclable reaction medium for the microwave-assisted, multi-component one-pot reactions of aromatic aldehydes with ethyl-2-cyanoacetate and 1,3- cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione in the presence of piperidine. This environmentally friendly microwave protocol offers ease of operation and enables recyclability of reaction medium and synthesis of a variety of substituted tetrahydrobenzo[b]pyran derivatives. It is an efficient, promising, and green synthetic strategy to construct tetrahydrobenzo[b]pyran skeleton. PMID: 21999654 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5341076 Sun, 23 Oct 2011 11:40:11 +0100 5341076 http://www.medworm.com/index.php?rid=5239767&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933110%26dopt%3DAbstract Authors: Zhou SM, Cheng L, Guo SJ, Zhu H, Tao SC Abstract Cell surfaces, especially mammalian cell surfaces, are heavily coated with complex poly- and oligosaccharides, and these glycans have been implicated in many functions, such as cell-to-cell communication, host-pathogen interactions and cell matrix interactions. Not surprisingly then, the aberrations of glycosylation are usually indicative of the onset of specific diseases, such as cancer. Therefore, glycans are expected to serve as important biomarkers for disease diagnosis and/or prognosis. Recent development of the lectin microarray technology has allowed researchers to profile the glycans in complex biological samples in a high throughput fashion. This relatively new tool is highly suitable for both live cell and cell lys... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5239767 Tue, 20 Sep 2011 04:00:00 +0100 5239767 http://www.medworm.com/index.php?rid=5215110&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902638%26dopt%3DAbstract Authors: Hagemeyer A, Volpe A PMID: 21902638 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215110 Fri, 09 Sep 2011 04:00:00 +0100 5215110 http://www.medworm.com/index.php?rid=5215109&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902639%26dopt%3DAbstract This article provides a number of concrete examples of EE systems, which have been designed and successfully implemented in studies, which focus on deriving reaction kinetic data. The implementation of high-throughput EE tools for performing kinetic studies of both catalytic and non-catalytic systems results in a significantly faster acquisition of high-quality kinetic modeling data, required to quantitatively predict the behavior of complex, multistep reactions. PMID: 21902639 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215109 Fri, 09 Sep 2011 04:00:00 +0100 5215109 http://www.medworm.com/index.php?rid=5215108&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902640%26dopt%3DAbstract Authors: Gruter GJ, Sipos L, Dam MA Abstract High Throughput experimentation has been well established as a tool in early stage catalyst development and catalyst and process scale-up today. One of the more challenging areas of catalytic research is polymer catalysis. The main difference with most non-polymer catalytic conversions is the fact that the product is not a well defined molecule and the catalytic performance cannot be easily expressed only in terms of catalyst activity and selectivity. In polymerization reactions, polymer chains are formed that can have various lengths (resulting in a molecular weight distribution rather than a defined molecular weight), that can have different compositions (when random or block co-polymers are produced), that can have cross-linking (ofte... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215108 Fri, 09 Sep 2011 04:00:00 +0100 5215108 http://www.medworm.com/index.php?rid=5215107&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902641%26dopt%3DAbstract Authors: Szesni N, Kaiser M, Putzien S, Fischer RW Abstract Supported Ionic Liquid Phase (SILP) catalysts have been prepared by effective immobilization of [Cu(TMEDA)(OH)]Cl in a nano-metric film of an ionic liquid on various oxidic support materials. The catalysts were tested for the oxidative homocoupling of 1-alkynes to the corresponding diynes in in a combined high throughput and conventional batch reaction approach. Among the screened support materials silica based materials performed best. The results indicate that for the specific reaction the thickness of the ionic liquids layer and therefore the mobility of the homogeneous copper complex within the ionic liquid layer as deduced from solid state nmr measurements have major impact on the catalytic performance. The optimized ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215107 Fri, 09 Sep 2011 04:00:00 +0100 5215107 http://www.medworm.com/index.php?rid=5215106&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902642%26dopt%3DAbstract Authors: Ravon U, Aguado S, Pawlesa J, Bergeret G, Tagliabue M, Zanardi S, Rizzo C, Paillaud JL, Farrusseng D Abstract Combinatorial screening using precipitation methods at room temperature can lead to a great diversity of carboxylate based Metal Organic Frameworks (MOFs) including already known or original porous solids. The investigation of the synthesis of MOFs in different solvent and solvent mixtures includes the use of solvents such as alcohols and tetrahydrofuran (THF) which would greatly facilitate large scale production. We also show the application of Principal Component Analysis (PCA) and clustering techniques on large libraries of XRD diffraction files in order to identify classes of similar phases and peculiar phases. The combinatorial screening of 105 samples in the ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215106 Fri, 09 Sep 2011 04:00:00 +0100 5215106 http://www.medworm.com/index.php?rid=5215105&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902643%26dopt%3DAbstract Authors: Lueangchaichaweng W, Geukens I, Peeters A, Jarry B, Launay F, Bonardet JL, Jacobs PA, Pescarmona PP Abstract Transition-metal-free oxides were studied as heterogeneous catalysts for the sustainable epoxidation of alkenes with aqueous H2O2 by means of High-Throughput Experimentation (HTE) techniques. A full-factorial HTE approach was applied in the various stages of the development of the catalysts: the synthesis of the materials, their screening as heterogeneous catalysts in liquid-phase epoxidation and the optimisation of the reaction conditions. Initially, the chemical composition of transition-metal-free oxides was screened, leading to the discovery of gallium oxide as a novel, active and selective epoxidation catalyst. On the basis of these results, the research line w... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215105 Fri, 09 Sep 2011 04:00:00 +0100 5215105 http://www.medworm.com/index.php?rid=5215104&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902644%26dopt%3DAbstract Authors: Wöelk HJ, Mestl G Abstract The oxidation of o-xylene and/or naphthalene to phthalic anhydride is one of the important industrial processes based on catalytic selective oxidation reactions. Vanadia - titania catalysts have been used in the industrial phthalic anyhdride process for the last 50 years. The operation parameters like the temperature range of operation, reactor inlet pressures, contact times, o-xylene loadings, etc. were constantly improved during this period of continuous process optimization so as to optimize catalyst performance and increase its life time. However, a fundamental understanding of the mutual interaction of the rather complex reaction network and the catalyst formulation is still missing. Recently, a detailed study of by-product formation as fun... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215104 Fri, 09 Sep 2011 04:00:00 +0100 5215104 http://www.medworm.com/index.php?rid=5215103&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902645%26dopt%3DAbstract Authors: Böhmer N, Roussiere T, Kuba M, Schunk SA Abstract Renewable feedstocks have been in the spotlight of intensive research activities over the past 10 years. Glycerol is one of the feedstock molecules which has been the target of numerous research efforts, for a number of reasons. First of all glycerol is currently readily available due to the fact that it is a couple product of the first generation biodiesel production. Secondly glycerol can be taken as a representative model substrate to explore the options of selective conversion of sugar alcohols to products of value. In our paper we discuss potential routes for the valorisation of glycerol which lead to intermediates already established within the petrochemical value chain and illustrate what impact high throughput expe... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215103 Fri, 09 Sep 2011 04:00:00 +0100 5215103 http://www.medworm.com/index.php?rid=5215102&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902646%26dopt%3DAbstract Authors: Mestl G Abstract The Temkin reactor concept was successfully extended to the high throughput operation mode and it could be considerably improved as compared to the original design with respect to an optimized gas flow pattern over the full size beads. This improved parallel reactor design was successfully used for the high throughput optimization of an innovative new class of physically coated VAM shell catalysts. Exploiting this novel, improved Temkin reactor concept allowed Süd-Chemie not only to optimize the multiparameter compositional space of noble metal and promoter loadings on the support spheres but for the first time to combine this "chemical optimization" with the high throughput improvement of catalytically decisive parameters as the active shell thickness, t... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215102 Fri, 09 Sep 2011 04:00:00 +0100 5215102 http://www.medworm.com/index.php?rid=5215101&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902647%26dopt%3DAbstract Authors: Szijjártó GP, Tompos A, Héberger K, Margitfalvi JL Abstract Effects of different catalyst components on the catalytic performance in steam reforming of ethanol have been investigated by means of Artificial Neural Networks (ANNs) and Partial Least Square regression (PLSR). The data base consisted of ca. 400 items (catalysts with varied composition), which were obtained from a former catalyst optimization procedure. Marten's uncertainty (jackknife) test showed that simultaneous addition of Ni and Co has crucial effect on the hydrogen production. The catalyst containing both Ni and Co provided remarkable hydrogen production at 450°C. The addition of Ceas modifier to the bimetallic NiCo catalyst has high importance at lower temperatures: the hydrogen concentration is doubl... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5215101 Fri, 09 Sep 2011 04:00:00 +0100 5215101 http://www.medworm.com/index.php?rid=5170452&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864291%26dopt%3DAbstract Authors: Roy A, McGee JE Abstract The section on patent review will be focused in the areas of interest to the readers of CCHTS. The search was conducted using the following key words: combinatorial chemistry, high throughput screening, drug repurposing, chemical library, high content screening, drug discovery and natural products. All patents highlighted here are identified by the patent number issued either by the World Intellectual Property Organization or by a regional patent office. PMID: 21864291 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5170452 Wed, 24 Aug 2011 23:00:00 +0100 5170452 http://www.medworm.com/index.php?rid=5170454&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21846324%26dopt%3DAbstract In this study, we further explored the binding modes of various types of inhibitors to CYP2D6 using a combination of ligand- and protein-based modeling approaches. Firstly, we developed and validated a pharmacophore model for CYP2D6 inhibitors, which consisted of two hydrophobic features and one hydrogen bond acceptor feature. Secondly, we constructed and validated a quantitative structure-activity relationship (QSAR) model for CYP2D6 inhibitors which gave a poor to moderate prediction accuracy. Thirdly, a panel of CYP2D6 inhibitors were subject to molecular docking into the active site of wild-type and mutated CYP2D6 enzyme. We demonstrated that 8 residues in the active site (Leu213, Glu216, Ser217, Gln244, Asp301, Ser304, Ala305, and Phe483) played an important role in the binding to the... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5170454 Tue, 16 Aug 2011 23:00:00 +0100 5170454 http://www.medworm.com/index.php?rid=5138375&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843140%26dopt%3DAbstract Comb Chem High Throughput Screen. 2011 Aug 16; Authors: Kundu B PMID: 21843140 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138375 Mon, 15 Aug 2011 23:00:00 +0100 5138375 http://www.medworm.com/index.php?rid=5138374&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843141%26dopt%3DAbstract Authors: Barua S, Ramos J, Potta T, Taylor D, Huang HC, Montanez G, Rege K Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated tra... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138374 Mon, 15 Aug 2011 23:00:00 +0100 5138374 http://www.medworm.com/index.php?rid=5138373&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843142%26dopt%3DAbstract Authors: Subramaniam S, Mehrotra M, Gupta D The emergence and spread of Plasmodium falciparum resistance to existing antimalarials emphasize the impelling search for novel drug targets and chemotherapeutic compounds. The ubiquitin-proteasome system plays a major role in overall protein turnover, in eukaryotic cells including plasmodia. 20S β subunit is the catalytic core of this proteolytic machinery, and hence most of the inhibitors developed are being targeted towards this component. Inhibition of the proteasome is established as a promising strategy to develop novel antimalarial drugs. The present study reports identification of novel drug-like 20S proteasome inhibitors with potential activity against the 20S β subunit of P. falciparum using a combination of ligand based (Support ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138373 Mon, 15 Aug 2011 23:00:00 +0100 5138373 http://www.medworm.com/index.php?rid=5138372&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843143%26dopt%3DAbstract Authors: Polgár T, Keserű GM In the last decade mass screening strategies became the main source of leads in drug discovery settings. Although high-throughput (HTS) and virtual screening (VS) realize the same concept the different nature of these lead discovery strategies (experimental vs. theoretical) results that they are typically applied separately. The majority of drug leads are still identified by hit-to-lead optimization of screening hits. Structural information on the target as well as on bound ligands, however, make structure-based and ligand-based virtual screening available for the identification of alternative chemical starting points. Although, the two techniques have rarely been used together on the same target, here we review the existing prominent studies on their tru... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138372 Mon, 15 Aug 2011 23:00:00 +0100 5138372 http://www.medworm.com/index.php?rid=5138371&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843144%26dopt%3DAbstract Authors: Sukumar N, Das S High-throughput in silico methods have offered the tantalizing potential to drastically accelerate the drug discovery process. Yet despite significant efforts expended by academia, national labs and industry over the years, many of these methods have not lived up to their initial promise of reducing the time and costs associated with the drug discovery enterprise, a process that can typically take over a decade and cost hundreds of millions of dollars from conception to final approval and marketing of a drug. Nevertheless structure-based modeling has become a mainstay of computational biology and medicinal chemistry, helping to leverage our knowledge of the biological target and the chemistry of protein-ligand interactions. While ligand-based methods utilize t... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138371 Mon, 15 Aug 2011 23:00:00 +0100 5138371 http://www.medworm.com/index.php?rid=5138369&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843145%26dopt%3DAbstract Authors: Garg V, Arora S, Gupta C Continued advancements in the area of technology have helped high throughput screening (HTS) evolve from a linear to parallel approach by performing system level screening. Advanced experimental methods used for HTS at various steps of drug discovery (i.e. target identification, target validation, lead identification and lead validation) can generate data of the order of terabytes. As a consequence, there is pressing need to store, manage, mine and analyze this data to identify informational tags. This need is again posing challenges to computer scientists to offer the matching hardware and software infrastructure, while managing the varying degree of desired computational power. Therefore, the potential of "On-Demand Hardware" and "Software as a Servi... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138369 Mon, 15 Aug 2011 23:00:00 +0100 5138369 http://www.medworm.com/index.php?rid=5138368&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843146%26dopt%3DAbstract Authors: Badrinarayan P, Sastry GN Drug discovery continues to be one of the greatest contemporary challenges and rational application of modelling approaches is the first important steps to obtain lead compounds, which can be optimised further. Virtual high-throughput screening (VHTS) is one of the efficient approaches to obtain lead structures for a given target. Strategic application of different screening filters like pharmacophore mapping, shape-based, ligand-based, molecular similarity etc., in combination with other drug design protocols provide invaluable insights in lead identification and optimization. Screening of large databases using these computational methods provides potential lead compounds, thus triggering a meaningful interplay between computations and experiments. I... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138368 Mon, 15 Aug 2011 23:00:00 +0100 5138368 http://www.medworm.com/index.php?rid=5138363&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843147%26dopt%3DAbstract Authors: Guido RV, Oliva G, Andricopulo AD The identification of promising hits and the generation of high quality leads are crucial steps in the early stages of drug discovery projects. The definition and assessment of both chemical and biological space have revitalized the screening process model and emphasized the importance of exploring the intrinsic complementary nature of classical and modern methods in drug research. In this context, the widespread use of combinatorial chemistry and sophisticated screening methods for the discovery of lead compounds has created a large demand for small organic molecules that act on specific drug targets. Modern drug discovery involves the employment of a wide variety of technologies and expertise in multidisciplinary research teams. The synergis... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5138363 Mon, 15 Aug 2011 23:00:00 +0100 5138363 http://www.medworm.com/index.php?rid=5087604&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21781027%26dopt%3DAbstract Authors: Shen C, Zhang L, Zhang G, Meng Q This paper reviews the functional polymer membrane and membrane based cell drug evaluation models for drug discovery. Based on the characteristics of biological membranes in vivo, chemical modification methods of synthetic membrane, including blending and surface modification are explored to mitigate the membrane fouling and improve biocompatibility. Different membrane-based cell models used in drug investigation and related trouble shooting are analyzed in detail. Specific attention is given to the current studies on ADME/Tox of drugs using membrane-based in vitro models of cells including Caco-2, hepatocytes or renal cells, which can be used to evaluate the feasibility of polymer membrane in drug investigation. The progress toward solving pre... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5087604 Sun, 24 Jul 2011 23:00:00 +0100 5087604 http://www.medworm.com/index.php?rid=5087603&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21781028%26dopt%3DAbstract Authors: Gao J, Ma L, Liu D, Wang Z In the post-genomic era, glycomics (the functional study of carbohydrates in living organisms) has come into the forefront of biological research because the interactions of glycoconjugates with proteins not only occur widely in biological processes of cells but also initiate infection of host cells by bacteria and viruses. Microarrays have been reportedly successful in carbohydrate-protein interaction as well as cellular surface glycan profiling. This review provides an overview of recent progress in the development of microarray-based techniques for glycomic studies. The fabrication, application and challenge/bottleneck of glycan/lectin microarrays have been summarized and discussed. PMID: 21781028 [PubMed - as supplied by publisher] (Source: C... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5087603 Sun, 24 Jul 2011 23:00:00 +0100 5087603 http://www.medworm.com/index.php?rid=5087606&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21774767%26dopt%3DAbstract Authors: Luesse SB, Wells G, Miller J, Bergmeier SC, McMills MC, Priestley ND, Wright DL The 7-oxabicyclo[2.2.1]heptene ring system is a common structural motif in many pharmacologically interesting molecules. We recognized the potential to employ this highly oxygenated and conformationally-restricted scaffold in diversity-oriented synthesis to generate a library of non-chiral but topologically complex compounds. Herein, we report the synthesis and biological evaluation of two 96-member tricyclic libraries containing the oxabicyclo[2.2.1]heptene framework using acetal formation as the key step. PMID: 21774767 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5087606 Wed, 20 Jul 2011 23:00:00 +0100 5087606 http://www.medworm.com/index.php?rid=5087605&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21774768%26dopt%3DAbstract Comb Chem High Throughput Screen. 2011 Jul 21; Authors: Hull C PMID: 21774768 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5087605 Wed, 20 Jul 2011 23:00:00 +0100 5087605 http://www.medworm.com/index.php?rid=5087607&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21774753%26dopt%3DAbstract Authors: Gozalbes R PMID: 21774753 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=5087607 Mon, 13 Jun 2011 23:00:00 +0100 5087607 http://www.medworm.com/index.php?rid=4945578&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21668408%26dopt%3DAbstract Authors: Roy A, McGee JE PMID: 21668408 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4945578 Mon, 13 Jun 2011 23:00:00 +0100 4945578 http://www.medworm.com/index.php?rid=4945577&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21668409%26dopt%3DAbstract Authors: Sabbaghan M, Alidoust M, Hossaini Z An efficient synthesis of 2-(dialkylamino)-4-phenyl)-1,3-thiazol-5-yl)(phenyl)methanone using acid chlorides, secondary amines, 2-bromoacethophenone and ammonium thiocyanate is described. PMID: 21668409 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4945577 Mon, 13 Jun 2011 23:00:00 +0100 4945577 http://www.medworm.com/index.php?rid=4896037&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631412%26dopt%3DAbstract Authors: Tai D, Chaguturu R, Fang J High throughput screening (HTS) has emerged as an important technique for allowing researchers to rapidly profile very large numbers of chemicals against drug targets. As recent and future advances make HTS cheaper to perform on even larger scales, the amount of data that has to be processed, analyzed, and searched will only grow larger in size and harder for researchers to manually sift through. It is therefore an unavoidable requirement that institutions utilizing HTS technology will need to begin looking for effective solutions in the maturing area of laboratory information management systems like many other types of labs have already done. K-Screen is one such solution. Our initial goal with K-Screen was to have an integrated application environm... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896037 Tue, 31 May 2011 23:00:00 +0100 4896037 http://www.medworm.com/index.php?rid=4896036&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631413%26dopt%3DAbstract Authors: Grandjean G, Graham R, Bartholomeusz G In recent years high throughput screening operations have become a critical application in functional and translational research. Although a seemingly unmanageable amount of data is generated by these high-throughput, large-scale techniques, through careful planning, an effective Laboratory Information Management System (LIMS) can be developed and implemented in order to streamline all phases of a workflow. Just as important as data mining and analysis procedures at the end of complex processes is the tracking of individual steps of applications that generate said data. Ultimately, the use of a customized LIMS will enable users to extract meaningful results from large datasets while trusting the robustness of their assays. To illustrate t... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896036 Tue, 31 May 2011 23:00:00 +0100 4896036 http://www.medworm.com/index.php?rid=4896035&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631414%26dopt%3DAbstract Authors: Hull C, Wray B, Winslow F, Vilicich M Every laboratory has a need to track and control the variables that drive the quality of the results. However, each laboratory is unique and what one organization deems to be a critical process to track and control will likely differ from other organizations. Furthermore, there is more than just the end product or result that needs to be tracked and controlled. All of the intermediate products and resources play a significant role in producing the final product and each of these needs to be included in the LIMS. At a high level, this article will present ideas and opinions on the following topics in relation to implementing a LIMS process tracking and control system in a laboratory: The difference between tracking and controlling processes... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896035 Tue, 31 May 2011 23:00:00 +0100 4896035 http://www.medworm.com/index.php?rid=4896034&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631415%26dopt%3DAbstract Authors: Lemmon V The Miami Project to Cure Paralysis, part of the University of Miami Miller School of Medicine, includes a laboratory devoted to High Content Analysis (HCA) of neurons. The goal of the laboratory is to uncover signaling pathways, genes, compounds, or drugs that can be used to promote nerve growth. HCA permits the quantification of neuronal morphology, including the lengths and numbers of axons. HCA of various libraries on primary neurons requires a team-based approach, a variety of process steps and complex manipulations of cells and libraries to obtain meaningful results. HCA itself produces vast amounts of information including images, well-based data and cell-based phenotypic measures. Documenting and integrating the experimental workflows, library data and extensi... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896034 Tue, 31 May 2011 23:00:00 +0100 4896034 http://www.medworm.com/index.php?rid=4896033&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631416%26dopt%3DAbstract We present a model for storage and exploitation of master data, practical applications of these techniques in the research context of small-molecule science, and specific benefits of MDM to small-molecule screening aimed at probe- and drug-discovery. PMID: 21631416 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896033 Tue, 31 May 2011 23:00:00 +0100 4896033 http://www.medworm.com/index.php?rid=4896039&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605065%26dopt%3DAbstract Authors: Lin L, Dong Y, Yang B, Zhao M The application of Isodon species in Chinese folk medicine has a long histroy, especially the ones called 'Xihuangcao' in Chinese. 'Xihuangcao' has been successfully applied to treat acute hepatitis, cholecystitis, enteritis, dysentery and trauma. The original species of 'Xihuangcao' is Isodon lophanthoides (Buch.-Ham.ex D.Don). However, there are five sources of Chinese medicinal herb 'Xihuangcao' due to their similar morphology and close pharmaceutical activity. Each source belongs to Isodon. However, their chemical composition and bioactivities are significantly different. In order to differentiate these sources of 'Xihuangcao' and to know their pharmaceutical effects, this review summarizes the chemical constituents, bioactive properties of 'X... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896039 Mon, 23 May 2011 23:00:00 +0100 4896039 http://www.medworm.com/index.php?rid=4896038&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605066%26dopt%3DAbstract Authors: Shin Y, Le H, Khojasteh C, Hop CE Metabolite identification study plays an important role in determining the sites of metabolic liability of new chemical entities (NCEs) in drug discovery for lead optimization. Here we compare the two predictive software, MetaSite and StarDrop, available for this purpose. They work very differently but are used to predict the site of oxidation by major human cytochrome P450 (CYP) isoforms. Neither software can predict non-CYP catalyzed metabolism nor the rates of metabolism. For the purpose of comparing the two software packages, we tested known probe substrate for these enzymes, which included 12 substrates of CYP3A4 and 18 substrates of CYP2C9 and CYP2D6 were analyzed by each software and the results were compared. It is possible that these ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896038 Mon, 23 May 2011 23:00:00 +0100 4896038 http://www.medworm.com/index.php?rid=4896045&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599622%26dopt%3DAbstract Authors: Zhou SM, Cheng L, Guo SJ, Zhu H, Tao SC Glycosylation is one of the most important posttranslational modification processes, which is regulated by a large number of enzymes. Cell surface, especially mammalian cell surface is heavily coated with glycans. Cell surface glycans are highly related to cell-cell communication, host-pathogen interaction, cell matrix interaction and etc. The aberrations of glycosylation, either intercellular or intracellular, usually indicate the onset of certain diseases, such as cancer and cancer metastasis, thus could be used as biomarkers. Lectin microarray, by far, is the most powerful technologies for high-throughput glycan profiling and comparison. It is highly suitable for both live cell and cell lysate analysis and has the potential for high-t... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896045 Thu, 19 May 2011 23:00:00 +0100 4896045 http://www.medworm.com/index.php?rid=4896044&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599623%26dopt%3DAbstract Authors: Jeannerat D, Furrer J State-of-the-art technologies and methodologies in NMR spectroscopy make it possible to obtain very informative and high-quality spectra in much less experimental time than classical methods by making better choices of NMR pulse sequences and acquisition parameters. This review presents some recent NMR methods allowing rapid identification, assignment and structural characterization of the components in mixtures. The relative merits of the different NMR pulse sequences are briefly discussed and recommendations are made for the preferred choice of sequences to obtain rapidly artifact-free data. This review covers diffusion experiments (DOSY), HSQC and HMBC experiments, ultra-resolved 2D spectra exploiting the property of aliasing and NOESY/ROESY experiment... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896044 Thu, 19 May 2011 23:00:00 +0100 4896044 http://www.medworm.com/index.php?rid=4896043&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599624%26dopt%3DAbstract Authors: De Moliner F, Banfi L, Riva R, Basso A The reaction of isocyanides with electron deficient alkynes has been first reported in 1969, about ten year after the first reports on the famous Ugi four component reaction. However it took about thirty years to realise that the zwitterionic intermediate originating by interaction of the two species could be trapped by a third component, thus giving the start to a novel class of isocyanide-based multicomponent reactions. From that first report dated 1996 there has been an ongrowing interest that has produced, so far, about 150 distinct scientific papers. This review is aimed at rationalising and cathegorising these reports and at offering an overview of all the possible applications of this novel methodology. PMID: 21599624 [PubMed -... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896043 Thu, 19 May 2011 23:00:00 +0100 4896043 http://www.medworm.com/index.php?rid=4896042&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599625%26dopt%3DAbstract Authors: Han P, Luan F, Gao Y, Wang J, Liu H A linear quantitative structure-visible light absorption wavelength (λ) relationship model for one hundred and forty-two photosensitizers was proposed using heuristic method and multiple linear regression analysis. The statistical parameters of the model were R2 = 0.916; F = 372.16; and RMSE = 5.0873. A fivefold cross-validation algorithm was applied, and the results indicated that the model has a satisfactory statistical stability and validity. The proposed model was evaluated for predictive ability with an external validation set, and the statistical parameters obtained were and R2EXT = 0.908; Q2EXT = 0.897; F = 118.14; and RMSEEXT = 5.6338 for the external test set. The results obtained demonstrated that the simple linear quantitative st... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896042 Thu, 19 May 2011 23:00:00 +0100 4896042 http://www.medworm.com/index.php?rid=4896041&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599626%26dopt%3DAbstract Authors: de Abreu MA, Alvaro-Benito M, Plou FJ, Fernández-Lobato M, Alcalde M β-Fructofuranosidases can divert their hydrolytic activity towards transglycosylation for the synthesis of high value-added products, including prebiotic fructooligosaccharides (FOS). A directed evolution strategy has been employed to enhance the transferase rate of the β-fructofuranosidase (SoINV) from the Schwanniomyces occidentalis yeast for the production of β-(2 β6)-linked FOS. To screen for transferase activity of the SoINV functionally expressed in Saccharomyces cerevisiae, a high-throughput screening protocol based on two colorimetric assays was validated (with coefficient of variance below 11%). Mutagenic libraries were constructed by error-prone PCR and clones showing higher glucose:fructose ra... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896041 Thu, 19 May 2011 23:00:00 +0100 4896041 http://www.medworm.com/index.php?rid=4896040&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21599627%26dopt%3DAbstract Authors: Sorimachi K, Nakamoto T All medicines pose a potential health risk, be they Eastern or Western medicines. Newly developed Western drugs must undergo rigorous testing to ensure their efficacy and safety, while with Eastern drugs, safety has generally been established because of their long histories of safe usage as traditional medicines. The regulation of Western medicines is much stronger than that of Eastern medicines, partly as pure chemicals are used and their effects and side effects are more likely to be acute. Eastern medicines consist of multiple components, generally extracted from a single or several plants or other natural sources, and their effects are not so acute, with delayed onset of side effects. However, the chronic usage of many Eastern medicines may result i... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4896040 Thu, 19 May 2011 23:00:00 +0100 4896040 http://www.medworm.com/index.php?rid=4850721&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592071%26dopt%3DAbstract Authors: Roy A, McGee JE The section on patent review will be focused in the areas of interest to the readers of CCHTS. The search was conducted using the following key words: combinatorial chemistry, high throughput screening, drug repurposing, chemical library, high content screening, drug discovery and natural products. All patents highlighted here are identified by the patent number issued either by the World Intellectual Property Organization or by a regional patent office. PMID: 21592071 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850721 Wed, 18 May 2011 23:00:00 +0100 4850721 http://www.medworm.com/index.php?rid=4850720&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592072%26dopt%3DAbstract Authors: Bak A, Magdziarz T, Kurczyk A, Polanski J A detailed knowledge of hydrogen bond geometry and its directional preferences is vital for in silico investigations of the ligand-receptor short-range non-covalent interactions. The spatial arrangement of the carbonyl and hydroxyl groups seems to determine the capability of β-ketoenol derivatives to recognize the surrounding environment by forming inter- and intra-molecular hydrogen bonds (IHB). In the current study we examined the application of the MoStBioDat platform for a massive database screening of the IHB motifs in β-ketoenol subunits (O=C-C=C-OH). Then, the virtual 3D structural data derived from ZINC and PubChem repository were compared to the experimentally determined CSD data. Differences specific for each database were ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850720 Wed, 18 May 2011 23:00:00 +0100 4850720 http://www.medworm.com/index.php?rid=4850726&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21564015%26dopt%3DAbstract This report demonstrates the strong impact in detection format on the success of a screening campaign and the importance of carefully designed confirmatory assays to eliminate those compounds that target the detection part of the assay. PMID: 21564015 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850726 Wed, 11 May 2011 23:00:00 +0100 4850726 http://www.medworm.com/index.php?rid=4850725&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21564016%26dopt%3DAbstract Authors: Simmons SO Whole-animal studies have been the mainstay of toxicity testing for decades. These approaches are too expensive and laborious to effectively characterize all of the chemicals currently in commercial use. In addition, there are social and ethical pressures to reduce, refine and replace animal testing in toxicology. The National Research Council (NRC) has outlined a new strategy to transition from animal-based tests to high-throughput, cell-based assays and computational modeling approaches to characterize chemical toxicants. Critical to this vision, assays that measure toxicity pathways associated with adverse health effects must be developed. Bioluminescent assays are particularly well suited to the demands of next-generation toxicity testing because they measure a ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850725 Wed, 11 May 2011 23:00:00 +0100 4850725 http://www.medworm.com/index.php?rid=4850724&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21564017%26dopt%3DAbstract Authors: Miraglia L, King F, Damoiseaux R The luminescent reporter gene assay (LRGA) is arguably the most prominent type of reporter gene assay used in biomolecular and pharmaceutical development laboratories. Part of this popularity is due to the high signal associated with luciferases, the foundation of this technology. This feature makes them ideally suited for high throughput screening applications where potentially millions of chemical compounds can be analyzed in a given assay. Recent technical advancements that enhance signal stability of the luciferases along with development and commercialization of multiple forms of luciferases, their respective substrates, and improvements in expression vectors for reporter gene assay (RGA) applications have broadened their use. While the pr... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850724 Wed, 11 May 2011 23:00:00 +0100 4850724 http://www.medworm.com/index.php?rid=4850723&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21564018%26dopt%3DAbstract Authors: Kokatam S, Pandey D, Gupta R, Krishna R, Soni R Angiogenesis is a promising area of research that targets key therapeutic areas like cancer; wound healing, inflammatory diseases, etc. There is an increasing demand for screening of potential angiogenic and anti-angiogenic agents using sensitive, robust cell-based assays. We have developed a reporter vector containing cis-acting elements that respond to growth factors/angiogenic ligands for use in a cell-based luciferase reporter assay.. We performed transient transfection of our reporter gene vector in MCF-7 cells to establish its application for screening of potential pro/anti-angiogenic agents. Reporter gene transactivation studies with different concentrations of fetal bovine serum clearly indicated that the vector is functi... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850723 Wed, 11 May 2011 23:00:00 +0100 4850723 http://www.medworm.com/index.php?rid=4850722&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21564019%26dopt%3DAbstract Authors: Larson B, Banks P, Shultz S, Sobol M, Cali JJ ADME-Tox testing examines the effects of an organism, tissue or cell on a compound, as well as the effects that the compound has on an organism, tissue or cell, and has gained in importance in the overall drug discovery process over the past twenty years. This is due to the rising percentage of drug candidate attrition in the 1990s and early 2000s due to adverse ADME/Tox profiles. The increased importance placed upon ADME/Tox testing has brought about new types of in-vitro assay technologies utilizing microplates to deliver the most pharmacologically relevant data. These tests, however, have typically been performed sequentially, where multiple assays over multiple microplates are used. This typically leads to increased time and co... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4850722 Wed, 11 May 2011 23:00:00 +0100 4850722 http://www.medworm.com/index.php?rid=4797296&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21534915%26dopt%3DAbstract Authors: Wang C, Wang L, Zhao C Research involving non-adherent cell lines, primary cells and blood cells is definitely important, but its application in image-based assays, especially in high-content systems, is highly limited. Accordingly, efficient high-content methods to study non-adherent cells are needed not only to improve diagnostics but also for early screening of targeted drugs. A plate-based assay using adhesion reagents for multiparametric measurement with single non-adherent and non-anchored cells in a large cell population in high-content cytometry was developed and optimized. The cells preserved their identity even during extensive biomanipulations. The proposed method is highly robust for better imaging and can be used in various assays in different cellular backgrounds... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797296 Sun, 01 May 2011 23:00:00 +0100 4797296 http://www.medworm.com/index.php?rid=4797295&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21534916%26dopt%3DAbstract In this study, we developed a triple addition calcium flux assay using FLIPR Tetra to identify multiple ligand classes for the metabotropic glutamate receptor 3 (mGlu3), using a cell line stably co-expressing the human G-protein-coupled mGlu3 receptor, a promiscuous G-protein (G(α16)), and rat Glast, a glutamate transporter. Compounds were added to the cells followed by stimulation with EC(10) and then EC(80) concentration of glutamate, the physiological agonist for mGlu receptors. This format produced a robust assay, facilitating the identification of agonists, positive allosteric modulators and antagonists/negative allosteric modulators. Follow up experiments were conducted to exclude false positives. Using this approach, we screened a library of approximately 800,000 compounds using FL... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797295 Sun, 01 May 2011 23:00:00 +0100 4797295 http://www.medworm.com/index.php?rid=4797294&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21534917%26dopt%3DAbstract Authors: Thorsen TS, Madsen KL, Dyhring T, Bach A, Peters D, Strømgaard K, Rønn LC, Gether U PDZ (PSD-95/Discs-large/ZO-1 homology) domains represent putative targets in several diseases including cancer, stroke, addiction and neuropathic pain. Here we describe the application of a simple and fast screening assay based on fluorescence polarization (FP) to identify inhibitors of the PDZ domain in PICK1 (protein interacting with C kinase 1). We screened 43,380 compounds for their ability to inhibit binding of an Oregon Green labeled C-terminal dopamine transporter peptide (OrG-DAT C13) to purified PICK1 in solution. The assay was highly reliable with excellent screening assay parameters (Z'≈0.7 and Z≈0.6). Out of ~200 compounds that reduced FP to less than 80% of the control wells,... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797294 Sun, 01 May 2011 23:00:00 +0100 4797294 http://www.medworm.com/index.php?rid=4797293&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21534918%26dopt%3DAbstract Authors: Bruno JG, Zuniga MA, Carrillo MP, Phillips T, Soll C Several different approaches have been taken to development of homogeneous fluorescent aptamer assays including end-labeled beacons and signaling aptamers which are intrinsically quenched by nucleotides. Two new strategies dubbed "intrachain" and "competitive" FRET-aptamer assays are summarize in this review. Intrachain and competitive FRET-aptamers can be engineered on the molecular level through a series exploratory experiments involving prior knowledge of aptamer secondary or tertiary structures and hypotheses about aptamer conformational changes. However, there is an intrinsic risk of altering aptamer affinity or specificity associated with chemical modifications of an aptamer. Natural selection methods for FRET-aptamers... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797293 Sun, 01 May 2011 23:00:00 +0100 4797293 http://www.medworm.com/index.php?rid=4797292&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21534919%26dopt%3DAbstract Authors: El Maatougui A, Silva AM, Coelho A An efficient solution-phase parallel procedure to perform the structural diversification of some formyl-nitrogen heterocycles (A) using the reusable TBD supported base is described. The library synthesis is based in a consecutive Alkylation-Knoevenagel functionalisation that uses alkyl halides (B), Michael acceptors (C) and activated methylene compounds (D) as diversity elements. PMID: 21534919 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797292 Sun, 01 May 2011 23:00:00 +0100 4797292 http://www.medworm.com/index.php?rid=4797303&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521148%26dopt%3DAbstract Authors: Luu TT, Malcolm NO, Nadassy K A pharmacophore is a model which represents the key physico-chemical interactions that mediate biological activity. There is a long history of using pharmacophore modeling methods to select subsets of compounds, focused towards a specific target of interest. This paper will review existing computational methods for deriving and comparing pharmacophore models. We outline a new classification of pharmacophore methods based on the abstraction of the underlying chemical interactions which embody a pharmacophore, and the methods available to quantitatively compare them. Within the context of this classification, example studies, using specific pharmacophore modelingmethods for focused library selection, will be discussed. PMID: 21521148 [PubMed - a... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797303 Mon, 25 Apr 2011 23:00:00 +0100 4797303 http://www.medworm.com/index.php?rid=4797302&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521149%26dopt%3DAbstract Authors: Gozalbes R, Pineda-Lucena A Chemoinformatics is a scientific discipline at the interface between chemistry and computer science, which nowadays is currently implemented in pharmaceutical companies as a part of the usual drug discovery pathway. Furthermore, taking into account the vast amount of experimental and computational data currently generated on drug discovery projects, the use of chemoinformatics tools has become increasingly necessary. Most of chemoinformatics projects are initiated from information stored in large databases of chemicals. The compounds are systematically characterized by numerical descriptors in order to manage this information and obtain some kind of chemical-biological relationships by similarity/diversity analysis, QSAR development for ADMET predic... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797302 Mon, 25 Apr 2011 23:00:00 +0100 4797302 http://www.medworm.com/index.php?rid=4797301&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521150%26dopt%3DAbstract Authors: Roy K, Mitra I Quantitative structure-activity relationships (QSARs) have important applications in drug discovery research, environmental fate modeling, property prediction, etc. Validation has been recognized as a very important step for QSAR model development. As one of the important objectives of QSAR modeling is to predict activity/property/toxicity of new chemicals falling within the domain of applicability of the developed models and QSARs are being used for regulatory decisions, checking reliability of the models and confidence of their predictions is a very important aspect, which can be judged during the validation process. One prime application of a statistically significant QSAR model is virtual screening for molecules with improved potency based on the pharmacopho... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797301 Mon, 25 Apr 2011 23:00:00 +0100 4797301 http://www.medworm.com/index.php?rid=4797300&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521151%26dopt%3DAbstract Authors: López-Vallejo F, Caulfield T, Martínez-Mayorga K, Giulianotti MA, Nefzi A, Houghten RA, Medina-Franco JL Virtual screening is increasingly being used in drug discovery programs with a growing number of successful applications. Experimental methodologies developed to speed up the drug discovery processes include high-throughput screening and combinatorial chemistry. The complementarities between computational and experimental screenings have been recognized and reviewed in the literature. Computational methods have also been used in the combinatorial chemistry field, in particular in library design. However, the integration of computational and combinatorial chemistry screenings has been attempted only recently. Combinatorial libraries (experimental or virtual) represent a no... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797300 Mon, 25 Apr 2011 23:00:00 +0100 4797300 http://www.medworm.com/index.php?rid=4797299&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521152%26dopt%3DAbstract This article is a review of the latest news in both experimental and in silico virtual screening in the fragment-based discovery field. Given the specificity of this journal, special attention will be given to fragment library design. PMID: 21521152 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797299 Mon, 25 Apr 2011 23:00:00 +0100 4797299 http://www.medworm.com/index.php?rid=4797298&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521153%26dopt%3DAbstract Authors: Liu T, Tang GW, Capriotti E The goal of computational protein structure prediction is to provide three-dimensional (3D) structures with resolution comparable to experimental results. Comparative modeling, which predicts the 3D structure of a protein based on its sequence similarity to homologous structures, is the most accurate computational method for structure prediction. In the last two decades, significant progress has been made on comparative modeling methods. Using the large number of protein structures deposited in the Protein Data Bank (~65,000), automatic prediction pipelines are generating a tremendous number of models (~1.9 million) for sequences whose structures have not been experimentally determined. Accurate models are suitable for a wide range of applications, ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797298 Mon, 25 Apr 2011 23:00:00 +0100 4797298 http://www.medworm.com/index.php?rid=4797297&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21521154%26dopt%3DAbstract This article describes examples of each of these design approaches and illustrates them with case studies, which highlight some of the issues and successes observed when screening target-focused libraries. PMID: 21521154 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4797297 Mon, 25 Apr 2011 23:00:00 +0100 4797297 http://www.medworm.com/index.php?rid=4687997&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470177%26dopt%3DAbstract Authors: Hou T PMID: 21470177 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687997 Fri, 01 Apr 2011 23:00:00 +0100 4687997 http://www.medworm.com/index.php?rid=4687996&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470178%26dopt%3DAbstract Authors: Rupp M, Körner R, Tetk IV The biopharmaceutical pro_le of a compound depends directly on the dissociation constants of its acidic and basic groups, commonly expressed as the negative decadic logarithm pKa of the acid dissociation constant (Ka). We survey the literature on computational methods to predict the pKa of small molecules. In this, we address data availability (used data sets, data quality, proprietary versus public data), molecular representations (quan-tum mechanics, descriptors, structured representations), prediction methods (approaches, implementations), as well as pKa-speci_c issues such as mono- and multiprotic compounds. We discuss advantages, problems, recent progress, and challenges in the field. PMID: 21470178 [PubMed - as supplied by publisher] (Sourc... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687996 Fri, 01 Apr 2011 23:00:00 +0100 4687996 http://www.medworm.com/index.php?rid=4687936&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470179%26dopt%3DAbstract Authors: Taboureau O, Jørgensen FS The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes. In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays. Significant progress has been made in structure-based and ligand-based drug design and a number of models have been developed to predict hERG blockage. Although ap... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687936 Fri, 01 Apr 2011 23:00:00 +0100 4687936 http://www.medworm.com/index.php?rid=4687897&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470180%26dopt%3DAbstract Authors: Zhu J, Wang J, Yu H, Li Y, Hou T Unfavorable oral bioavailability is an important reason accounting for the failure of the drug candidates. Considering the lack of in vitro high-throughput screening assay for oral bioavailability, it is critical to develop in silico models for early predictions of oral bioavailability. In this review, we summarize present knowledge and recent progress related to the in silico prediction of oral bioavailability, including the current available datasets of oral bioavailability in human, the roles of physiochemical properties contributing to oral bioavailability, and the available theoretical models to predict oral bioavailability. Particularly, the regression model recently developed by us was demonstrated, which is based on the largest dataset ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687897 Fri, 01 Apr 2011 23:00:00 +0100 4687897 http://www.medworm.com/index.php?rid=4687862&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470181%26dopt%3DAbstract Authors: Zhang T, Chen Q, Li L, Liu LA, Wei DQ The application of combinatorial chemistry and high-throughput screening technique enables the large number of chemicals to be generated and tested simultaneously, which will facilitate the drug development and discovery. At the same time, it brings about a challenge of how to efficiently identify the potential drug candidates from thousands of compounds. A way used to deal with the challenge is to consider the drug pharmacokinetic properties, such as absorption, distribution, metabolism and excretion (ADME), in the early stage of drug development. Among ADME properties, metabolism is of importance due to the strong association with efficacy and safety of drug. The review will focus on in silico approaches for prediction of Cytochrome P450... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687862 Fri, 01 Apr 2011 23:00:00 +0100 4687862 http://www.medworm.com/index.php?rid=4687857&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470182%26dopt%3DAbstract Authors: Wang J, Hou T Aqueous solubility is one of the major physiochemical properties to be optimized in drug discovery. It is related to absorption and distribution in the ADME-Tox (Absorption, Distribution, Metabolism, Excretion, and Toxicity). Aqueous solubility and membrane permeability are the two key factors that affect a drug's oral bioavailability. Because of the importance of aqueous solubility, a lot of efforts have been spent on developing reliable models to predict this physiochemical property. Although some progress has been made and a lot of models have been constructed, it is concluded that accurate and reliable aqueous models targeted to predict solubility of drug-like molecules, have not emerged based on the outcome of an aqueous solubility prediction campaign sponso... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687857 Fri, 01 Apr 2011 23:00:00 +0100 4687857 http://www.medworm.com/index.php?rid=4687856&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470183%26dopt%3DAbstract Authors: Geerts T, Vander Heyden Y The accurate prediction of the in-vivo pharmacokinetics of a new potential drug compound based on only its virtual structure is the ultimate goal of in-silico ADME-Tox property modeling. A comprehensive review is made on recent studies concerning the A (absorption) in ADME-Tox, i.e. the in-silico modeling of both Caco-2 permeability and human intestinal absorption. The data sets used, the descriptors selected to build the models, the variable selection methods, the modeling techniques and the performed model validation are critically discussed. It was concluded that reliable models which improve the success rate of compound selection and drug development are still lacking. Limiting the quality of the models are, for instance, inappropriate compilation... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687856 Fri, 01 Apr 2011 23:00:00 +0100 4687856 http://www.medworm.com/index.php?rid=4687855&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470184%26dopt%3DAbstract Authors: Mohan CG Computational tools for predicting toxicity have been envisioned to have the potential to broadly impact up on the attrition rate of compounds in pre-clinical drug discovery and development. An integrated approach of computer-assisted, predictive, and physico-chemical properties of a compound, along with its in vitro and in vivo analysis, needs to be routinely exercised in the lead identification and lead optimization processes. Starting with a good lead can save a lot of money and it can significantly reduce the entire drug discovery process. The journey towards triple R's- reduce, replace and refine, further proves to be successful in predicting adverse drug reactions in patients (or animals) enrolled in clinical trials. However, the impact of predictive toxicity an... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687855 Fri, 01 Apr 2011 23:00:00 +0100 4687855 http://www.medworm.com/index.php?rid=4687854&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470185%26dopt%3DAbstract Authors: Delisle RK, Otten J, Rhodes S Cytochrome P450 enzymes are the predominant mediators of phase I metabolism of exogenous small molecules. As a result of their extensive role in metabolism of xenobiotics, drug compounds, and endogenous compounds, as well as their wide tissue distribution, significant drug discovery resources are spent to avoid interacting with this class of enzymes. Here we review historical and recent in silico modeling of 7 cytochrome P450 enzymes of particular interest, specifically CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. For each we provide a brief biological background including known inhibitors, substrates, and inducers, as well as details of computational modeling efforts and advances in structural biology. We also provide similar deta... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4687854 Fri, 01 Apr 2011 23:00:00 +0100 4687854 http://www.medworm.com/index.php?rid=4570408&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375500%26dopt%3DAbstract Authors: Roy A The section on patent review will be focused in the areas of interest to the readers of CCHTS. The search was conducted using the following key words: combinatorial chemistry, high throughput screening, drug repurposing, chemical library, high content screening, drug discovery and natural products. All patents highlighted here are identified by the patent number issued either by the World Intellectual Property Organization or by a regional patent office. PMID: 21375500 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4570408 Mon, 07 Mar 2011 00:00:00 +0100 4570408 http://www.medworm.com/index.php?rid=4570407&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375501%26dopt%3DAbstract Authors: Gupta VK, Agarwal AN, Singhal B Prime concerns with modern developments are attributed to high level undetected but important biological substances or even toxicants cycled often among individual and populations; which in turn agonizes environmental monitoring, trace-gas detection, water treatment facilities, in vivo detection in biological fluids and other accomplishments. For the detection of such analytes, several analytical devices combined with biological compopnent have been designed with a physiochemical detector component. Here, we essentially focus on drug-based potentiometric membrane sensors known as ion selective electrodes (ISEs). The functionality of ion-selective membrane is quite intricate, challenging, and our undertsanding is yet to be thrived with more inter... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4570407 Mon, 07 Mar 2011 00:00:00 +0100 4570407 http://www.medworm.com/index.php?rid=4570406&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375502%26dopt%3DAbstract Authors: Sedlák D, Paguio A, Bartůněk P Steroid hormone receptors represent a major target in drug discovery. As ligand inducible transcription factors, their activity can be modulated by small lipophilic molecules. Here we describe two panels of potent and selective luciferase reporter cell lines based on cells with low endogenous steroid receptor activity (U2OS). The panels contain reporter cell lines for estrogen receptors α and β, androgen, glucocorticoid, mineralocorticoid, and progesterone receptors. In the first panel, the activation of either synthetic, steroid response elements containing promoter or viral promoter is mediated by full-length steroid receptors. The second panel is based on the expression of the chimeric receptor, which was created by the replacement of the... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4570406 Mon, 07 Mar 2011 00:00:00 +0100 4570406 http://www.medworm.com/index.php?rid=4570405&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375503%26dopt%3DAbstract Authors: Galvez J, Villar VM, Galvez-Llompart M, Amigó JM Molecular topology can be considered an application of graph theory in which the molecular structure is characterized through a set of graph-theoretical descriptors called topological indices. Molecular topology has found applications in many different fields, particularly in biology, chemistry, and pharmacology. The first topological index was introduced by H. Wiener in 1947 [1]. Although its very first application was the prediction of the boiling points of the alkanes, the Wiener index has demonstrated since then a predictive capability far beyond that. Along with the Wiener index, in this paper we focus on a few pioneering topological indices, just to illustrate the connection between physicochemical properties and molecula... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4570405 Mon, 07 Mar 2011 00:00:00 +0100 4570405 http://www.medworm.com/index.php?rid=4570404&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375504%26dopt%3DAbstract Authors: Zdrenghea UV, Tomoaia G, Pop-Toader DV, Mocanu A, Horovitz O, Tomoaia-Cotisel M The procaine effect on human erythrocytes was investigated by atomic force microscopy (AFM) at three procaine concentrations, about 5 x 10(-7) M, 5 x 10(-5) M and 5 x 10(-4) M. The changes in surface morphology of erythrocyte membrane bring direct evidence on the procaine effect on the cell membrane at micro- and nanometer scale. AFM images of the control erythrocytes (without procaine) showed a well defined concave (donut) shape of cells. The structure of control erythrocytes membrane is featured by closely packed nanometer size intra-membranous particles. After the incubation of the fresh blood with increasing procaine concentrations, a progressive increase in both concave depth and surface rough... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4570404 Mon, 07 Mar 2011 00:00:00 +0100 4570404 http://www.medworm.com/index.php?rid=4456769&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271980%26dopt%3DAbstract Authors: Yan B PMID: 21271980 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456769 Wed, 26 Jan 2011 00:00:00 +0100 4456769 http://www.medworm.com/index.php?rid=4456768&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271981%26dopt%3DAbstract The objective of this paper is to examine the challenges and opportunities in high throughput screening of atomic scale chemistry via a technique known as atom probe tomography. While there are numerous methods that exist in the field of throughput screening, even at the nanoscale, most of the effort is on screening properties , rather than chemistry and/or structure. In this overview, we discuss the role atom probe tomography can have as a high throughput screening tool of atomic scale chemistry. Particular emphasis on the study of organic/ biological materials is given along with the needs and challenges to make atom probe tomography more widespread in the field of combinatorial chemistry. PMID: 21271981 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Th... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456768 Wed, 26 Jan 2011 00:00:00 +0100 4456768 http://www.medworm.com/index.php?rid=4456767&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271982%26dopt%3DAbstract Authors: Liu Y, Yan B Chemical modifications of nanoparticle's (NP's) surfaces can be used to regulate their activities, remove their toxic effects, and enable them to perform desired functions. Similar to SPS samples, modified NPs also have small-molecules on the surface of a solid support. The need to monitor synthesis, optimize reaction conditions, and characterize the products is quite similar in both situations. FTIR, NMR, MS and other analytical methods have been used as effective methods to analyze surface bound molecules and monitor organic reactions directly, or indirectly, on a solid phase of a resin or a NPs. PMID: 21271982 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456767 Wed, 26 Jan 2011 00:00:00 +0100 4456767 http://www.medworm.com/index.php?rid=4456766&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271983%26dopt%3DAbstract Authors: Liang N, Zhang B Due to the unique properties, such as their large surface to volume ratio and easy modification, nanomaterials have recently been studied as effective sorbents in the field of separation science. It has proven to be more effective and efficient to use nanoparticles (NPs) as a stationary phase in solid-phase extraction separation. In addition, NPs can be also used as buffer additives in capillary electrophoresis separation. This review highlights recent developments in high-throughput separation methodologies employing nanomaterials such as carbon nanotubes, gold nanoparticles and magnetic NPs etc. PMID: 21271983 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456766 Wed, 26 Jan 2011 00:00:00 +0100 4456766 http://www.medworm.com/index.php?rid=4456763&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271984%26dopt%3DAbstract Authors: Dong CM Over the past two decades, glycosylated nanoparticles (i.e., glyconanoparticles having sugar residues on the surface) received much attention for biomedical applications such as bioassays and targeted drug delivery. This minireview focuses on three aspects: (1) glycosylated gold nanoparticles, (2) glycosylated quantum dots, and (3) glyconanoparticles self-assembled from amphiphilic glycopolymers. The synthetic methods and the multivalent interactions between glyconanoparticles and lectins is shortly illustrated. PMID: 21271984 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456763 Wed, 26 Jan 2011 00:00:00 +0100 4456763 http://www.medworm.com/index.php?rid=4456762&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21271985%26dopt%3DAbstract Authors: Sun S, Ding J, Bao J, Luo Z, Gao C The last decade has seen significant progresses in the application of combinatorial approaches and high-throughput screening in photocatalyst discovery. This paper aims at providing a comprehensive review on the parallel synthesis and high-throughput characterization of photocatalysts, including the development of instrumentation, strategy of experiment, preparation of libraries, high-throughput screening technique and data analysis. The review ends with a summary of the remaining challenges and prospects on combinatorial photocatalyst discovery. PMID: 21271985 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456762 Wed, 26 Jan 2011 00:00:00 +0100 4456762 http://www.medworm.com/index.php?rid=4456761&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21275889%26dopt%3DAbstract Authors: Fourches D, Pu D, Tropsha A Evaluation of desired and undesired, biological effects of Manufactured NanoParticles (MNPs) is of critical importance for the future of nanotechnology. Experimental studies, especially toxicological, are time-consuming and costly, calling for the development of efficient computational tools capable of predicting biological events caused by MNPs from their structure and physical chemical properties. This mini-review assesses the potential of modern cheminformatics methods such as Quantitative Structure - Activity Relationship modeling to develop statistically significant and externally predictive models that can accurately forecast biological effects of MNPs from the knowledge of their physical, chemical, and geometrical properties. We discuss major... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456761 Wed, 26 Jan 2011 00:00:00 +0100 4456761 http://www.medworm.com/index.php?rid=4456760&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21275890%26dopt%3DAbstract We describe in details new emerging analytical tools compatible with nanostructured surfaces, analyzing different possible strategies, depending on the objective of the experiment and on the library format. PMID: 21275890 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4456760 Wed, 26 Jan 2011 00:00:00 +0100 4456760 http://www.medworm.com/index.php?rid=4268881&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143178%26dopt%3DAbstract Authors: Chatterjee K, Young MF, Simon CG Optimizing cell-material interactions is critical for maximizing regeneration in tissue engineering. Combinatorial and high-throughput (CHT) methods can be used to systematically screen tissue scaffolds to identify optimal biomaterial properties. Previous CHT platforms in tissue engineering have involved a two-dimensional (2D) cell culture format where cells were cultured on material surfaces. However, these platforms are inadequate to predict cellular response in a three-dimensional (3D) tissue scaffold. We have developed a simple CHT platform to screen cell-material interactions in 3D culture format that can be applied to screen hydrogel scaffolds. Herein we provide detailed instructions on a method to prepare gradients in elastic modulus of ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4268881 Tue, 14 Dec 2010 00:00:00 +0100 4268881 http://www.medworm.com/index.php?rid=4268880&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143179%26dopt%3DAbstract Authors: Regberg T, Lindquist C, Pilotti A, Ellström C, Fägerstam L, Eckersten A, Shinohara Y, Gallion SL, Hogan JC Spatially addressable combinatorial libraries were synthesized by solution phase chemistry and screened for binding to human serum albumin. Members of arylidene diamide libraries were among the best hits found, having submicromolar binding affinities. The results were analyzed by the frequency with which particular substituents appeared among the most potent compounds. After immobilization of the ligands either through the oxazolone or the amine substituent, characterization by surface plasmon resonance showed that ibuprofen affected the binding kinetics, but phenylbutazone did not. It is therefore likely that these compounds bind to Site 2 in sub domain IIIA of human s... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4268880 Tue, 14 Dec 2010 00:00:00 +0100 4268880 http://www.medworm.com/index.php?rid=4268879&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143180%26dopt%3DAbstract Authors: Díaz-Ortiz A, de la Hoz Jesús Alcázar A, Carrillo JR, Herrero MA, Fontana A, de M Muñoz J, Prieto P, de Cózar A Organic reactions performed in the absence of solvent in domestic ovens without appropriate temperature control are generally considered as not reproducible, particularly when different instruments are used. For this reason, reproducibility has historically been one of the major issues associated with Microwave-Assisted Organic Synthesis (MAOS) especially when domestic ovens are involved. The lack of reproducibility limits the general applicability and the scale up of these reactions. In this work several solvent-free reactions previously carried out in domestic ovens have been translated into a single-mode microwave reactor and then scaled up in a multimode ove... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4268879 Tue, 14 Dec 2010 00:00:00 +0100 4268879 http://www.medworm.com/index.php?rid=4268878&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143181%26dopt%3DAbstract Authors: Urbano-Cuadrado M, Rabal O, Oyarzabal J Due to the huge amount of data generated in drug discovery programs, their success strongly depends on both the workflows and platforms to manage and, more importantly, to integrate different chemical and biological data sources. At Experimental Therapeutics Program in the Spanish National Cancer Research Center (CNIO), we have addressed our efforts in the design and optimal implementation of those key processes that enable dynamic workflows and interfaces between the different information blocks. Our approach focuses on the development of a common chemical and biological repository (CCBR) that gathers all data that pass quality control criteria. An integral web application (WACBIP) was designed to query against CCBR while providing deci... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4268878 Tue, 14 Dec 2010 00:00:00 +0100 4268878 http://www.medworm.com/index.php?rid=4268877&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143187%26dopt%3DAbstract Authors: Zhou P PMID: 21143187 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4268877 Wed, 01 Dec 2010 00:00:00 +0100 4268877 http://www.medworm.com/index.php?rid=4245738&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118078%26dopt%3DAbstract Authors: Kasemsook S, Stecher G, Fuchsberger C, Abel G, Popp M, Bonn GK The major concern of the present article is research into the combination of analytical assessment and multi-correlative data interpretation. For this purpose, a high performance liquid chromatography (HPLC) procedure was developed for the simultaneous quantification of salicin, salicylalcohol derivatives, phenolic acids, flavonoids, and monomeric catechins after solid phase extraction (SPE). On the basis of an established and validated HPLC method, 49 different Salix samples were extracted, purified, and analysed. Furthermore, the quantity of total polyphenols (Folin-Ciocalteau colorimetric reaction) and the antioxidant activity (DPPH radical scavenging activity test) were determined and correlated. This yielded c... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245738 Mon, 29 Nov 2010 00:00:00 +0100 4245738 http://www.medworm.com/index.php?rid=4245737&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118079%26dopt%3DAbstract Authors: Cozzolino D Chemical and physiological properties are related to individual or bioactive compounds such as essential oils, terpenoids, flavonoids, volatile compounds and other chemicals which are present in natural products in low concentrations (e.g. ppm or ppb). For many years, classical separation, chromatographic and spectrometric techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), liquid chromatography (LC) and mass spectrometry (MS) have been used for the elucidation of isolated compounds from different matrices. Hence, the use of standard separation, chromatographic and spectrometric methods was found useful in chemical and both plant and animal physiology studies, for fingerprinting and comparing natural and synthetic samples, as ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245737 Mon, 29 Nov 2010 00:00:00 +0100 4245737 http://www.medworm.com/index.php?rid=4245736&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118080%26dopt%3DAbstract We describe a high-throughput screen of a proprietary library of 5016 drug-like compounds against three prokaryotic NAT enzymes and two eukaryotic NAT enzymes. PMID: 21118080 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245736 Mon, 29 Nov 2010 00:00:00 +0100 4245736 http://www.medworm.com/index.php?rid=4245735&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118081%26dopt%3DAbstract Authors: Buchstaller HP, Anlauf U A straightforward and effective procedure for the solution phase preparation of a 2-aminothiazole combinatorial library is described. Reaction, work-up and isolation of the title compounds as free bases was accomplished in a fully automated fashion using the Chemspeed ASW 2000 automated synthesizer. The compounds were obtained in good yields and excellent purities without any further purification procedure. PMID: 21118081 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245735 Mon, 29 Nov 2010 00:00:00 +0100 4245735 http://www.medworm.com/index.php?rid=4245734&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118082%26dopt%3DAbstract Authors: Pai R, Pai A, Srivastava B, Kohli K Powder layering technique was evaluated using laboratory scale centrifugal granulator instrument to prepare extended release pellet dosage form of ketoprofen. Ethyl cellulose and shellac polymers were used for drug layering and extended release coating in the same apparatus. Inert sugar spheres were intermittently treated with drug powder and binding solution. Combination of ethyl cellulose (45cps) and shellac was evaluated as binders at different levels (1:3 ratio, at 6%, 12%, 16% and 21%w/w polymer) for drug loading and for extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer). Pellets were evaluated for drug release study using paddle apparatus in pH 6.8 Phosphate buffer, 900ml at 100 rpm. Ethyl cellulose and shellac when used... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245734 Mon, 29 Nov 2010 00:00:00 +0100 4245734 http://www.medworm.com/index.php?rid=4245733&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118083%26dopt%3DAbstract Authors: Woodard SS, Jerome KD Combinatorial cyclizations of imidates and hydrazides with methylene linked R groups, generated from the corresponding nitriles and carboxylic acids, respectively, provided a large library of 3,5-dimethylene substituted 1,2,4-trizoles. PMID: 21118083 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245733 Mon, 29 Nov 2010 00:00:00 +0100 4245733 http://www.medworm.com/index.php?rid=4245732&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21118084%26dopt%3DAbstract Authors: Xin GZ, Zhou JL, Qi LW, Li P Natural products (NPs) are combinatorial chemical libraries with diversities in chemical structures and pharmacological activities. Screening active compounds is in many cases an important factor in drug discovery. It was not easy to screen out the bioactive compounds from complex extracts consisting of many NPs. Development of rapid, effective and accurate methods is in high demand. During last decades, mass spectrometry (MS)-based strategies, combining isolation, structures, and bioactivity in a single run, were programmed in the NPs screening. The current article reviews different assay formats and applications of MS-based methods for screening of active NPs. This review is divided into three sections based on methods classification. The first p... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4245732 Mon, 29 Nov 2010 00:00:00 +0100 4245732 http://www.medworm.com/index.php?rid=4087497&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958252%26dopt%3DAbstract This study demonstrated the utility of ANNs as QSAR models for pre-screening of potential endocrine disruptors. PMID: 20958252 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087497 Tue, 19 Oct 2010 23:00:00 +0100 4087497 http://www.medworm.com/index.php?rid=4087496&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958253%26dopt%3DAbstract Authors: Ozen T, Darcan C, Aktop O, Turkekul I The antioxidative activity of the methanol extracts obtained from twelve commonly consumed wild edible mushrooms was determined according to the phosphomolybdenum method, inhibition of linoleic acid peroxidation, reducing power, metal chelating, O(2)(˙-), DPPH(˙), peroxide and H(2)O(2) scavenging activity, and compared to standard antioxidant compounds such as a-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and trolox wildly grown in the Black Sea Region of Turkey. Total phenolic compounds, flavonoids, anthocyanins, ascorbic acid, b-carotene and lycopene in the extracts were measured. The antimicrobial activities of extracts were also evalated against gram (-) and (+) bacteria and yeast with disc diffusion m... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087496 Tue, 19 Oct 2010 23:00:00 +0100 4087496 http://www.medworm.com/index.php?rid=4087495&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958254%26dopt%3DAbstract Authors: Castro AA, Aucélio RQ, Rey NA, Miguel EM, Farias PA This paper describes a stripping method for the determination of nevirapine at the submicromolar concentration levels The method is based on controlled adsorptive accumulation of nevirapine at thin-film mercury electrode, followed by a linear cyclic scan voltammetry measurement of the surface species. Optimal experimental conditions include a 2.0 x 10-3 mol L-1 NaOH solution (supporting electrolyte), an accumulation potential of -0.20 V, and a scan rate of 100 mV s-1. The response of nevirapine is linear over the concentration range 0.01 - 0.14 ppm. For an accumulation time of 6 minutes, the detection limit was found to be 0.87 ppb (3.0 x 10- 9 mol L-1). More convenient methods to measure the nevirapine in presence of the ef... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087495 Tue, 19 Oct 2010 23:00:00 +0100 4087495 http://www.medworm.com/index.php?rid=4087494&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958255%26dopt%3DAbstract Authors: Prodanovic R, Ostafe R, Scacioc A, Schwaneberg U A compartmentalized tyramid labeling system (CoaTi) employing flow cytometry for sorting of yeast cells was developed as ultrahigh-throughput screening for Glucose oxidase (GOx) from Aspergillus niger. CoaTi combines in vitro compartmentalization technology with the CARD reporter system which uses fluorescein tyramide labels for detection of peroxidase activity. Physical connection between cells and fluorescein tyramide radicals was achieved by compartmentalization of yeast cells inside microdroplets of single water-in-oil emulsions. After reaction cells were recovered from single emulsions and sorted by flow cytometry. An error prone PCR mutant library of Glucose oxidase (GOx) containing 10(7) cells and ≈10(5) of different GO... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087494 Tue, 19 Oct 2010 23:00:00 +0100 4087494 http://www.medworm.com/index.php?rid=4087493&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958256%26dopt%3DAbstract Authors: Lau D, Hay DG, Hill MR, Muir BW, Furman SA, Kennedy DF This paper reports on a systematic method - called PLUXter - developed for screening and data mining of large numbers of potential metal-organic framework compounds that have been synthesized then subsequently analyzed with high throughput synchrotron radiation X-ray powder diffraction. The first part of the method utilizes principal components analysis (PCA), which allows materials to be ranked in order of crystallinity so that undesirable amorphous materials may be identified and eliminated. The second part allows structural grouping within and between samples to be observed using hierarchical cluster analysis (HCA). Classification using a single linkage distance produced unsatisfactory clusters however the dendrogram's ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087493 Tue, 19 Oct 2010 23:00:00 +0100 4087493 http://www.medworm.com/index.php?rid=4087492&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958257%26dopt%3DAbstract Authors: Rajasärkkä J, Virta M A panel of luminescent Saccharomyces cerevisiae cell-based nuclear receptor assays, consisting of human estrogen receptors α and β, androgen receptor, and aryl hydrocarbon receptor, was miniaturized from the standard 96-well microplate format to high-throughput 384- and 1536-well microplate formats. In these assays, firefly luciferase lacking the peroxisome targeting sequence was used as a reporter and D-luciferin substrate was pre-mixed with the yeast cells before the incubation step, eliminating cell lysis and substrate addition steps, and allowing multiple readings at any desired time point. All of the assays were highly functional in the 384-well format, and most functioned well in the 1536-well format. The detection limit of the estrogen receptor... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087492 Tue, 19 Oct 2010 23:00:00 +0100 4087492 http://www.medworm.com/index.php?rid=4087491&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958258%26dopt%3DAbstract Authors: Musumarra G, Condorelli DF, Fortuna CG OPLS discriminant analysis (OPLS-DA) was successfully applied for the selection of a limited number of gene transcripts necessary to discriminate PTPN11 and RAS mutated cells in acute lymphoblastic leukaemia (ALL) patients. The original set of 273 variables with VIP (1) values higher than 2.0 in the OPLS-DA model could be further reduced to 200 by elimination of less informative variables in the PCA class models adopted for SIMCA classification. The above 200 transcripts not only achieve a satisfactory discrimination accuracy between PTPN11 and RAS mutated cells but also indicate clearly that wild type samples belong to none of the mutated class models. In this list it was possible to identify candidate genes that could be involved in the... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087491 Tue, 19 Oct 2010 23:00:00 +0100 4087491 http://www.medworm.com/index.php?rid=4087490&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958259%26dopt%3DAbstract Authors: Liu Y, Zhang Y In this paper we propose a matrix depiction and two new invariants of DNA sequences. This approach is illustrated on the primate mitochondrial DNA sequences for 11 different species and 80 different H5N1 avian influenza virus DNA sequences. We also construct the dendrogram tree for them. These phylogenies obtained are generally consistent with evolutionary trees constructed in previous studies. PMID: 20958259 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087490 Tue, 19 Oct 2010 23:00:00 +0100 4087490 http://www.medworm.com/index.php?rid=4087489&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20958260%26dopt%3DAbstract This study demonstrates the value of in vivo screening of fluorescently labeled phage for the prediction of the efficacy of the corresponding 111In-labeled synthetic peptide as an in vivo SPECT tumor imaging agent. PMID: 20958260 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4087489 Tue, 19 Oct 2010 23:00:00 +0100 4087489 http://www.medworm.com/index.php?rid=4039225&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883186%26dopt%3DAbstract Authors: Alaerts G, Dejaegher B, Smeyers-Verbeke J, Heyden YV The use of chromatographic fingerprints from herbal products is an approach in which the whole chromatographic profile is applied to evaluate the quality of the investigated product. In this paper, recent developments in the set-up and data analysis of chromatographic fingerprints for herbal products are discussed. First different set-ups for fingerprint development are reviewed. Prior to fingerprint development, a suitable sample preparation, e.g. extraction, should be considered. In a second instance, this review focuses on the data analysis used for the different applications of fingerprints. Chemometric pretreatment of the data is usually necessary and is introduced first, followed by a short overview of the data handlin... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039225 Wed, 29 Sep 2010 23:00:00 +0100 4039225 http://www.medworm.com/index.php?rid=4039223&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883187%26dopt%3DAbstract Authors: Sertel S, Plinkert PK, Efferth T The epidermal growth factor receptor (EGFR) has become an important molecular target in cancer therapy. Various small molecules and therapeutic antibodies targeting EGFR family members have been developed during recent years and are established in clinical oncology. However, increasing clinical application of EGFR tyrosine kinase inhibitors has resulted in the development of resistance to EGFR-targeting drugs due to the selection of EGFR-mutated variants. This phenomenon forced the search for novel EGFR inhibitors with activity towards EGFR-mutant tumors. This review describes recent achievements in natural products derived from medicinal plants as novel EGFR inhibitors. PMID: 20883187 [PubMed - as supplied by publisher] (Source: Combinator... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039223 Wed, 29 Sep 2010 23:00:00 +0100 4039223 http://www.medworm.com/index.php?rid=4039222&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883188%26dopt%3DAbstract Authors: Wu S, Liang J Counter-current chromatography (CCC) is a unique support-free liquid-liquid partition chromatography winning wide applications in the separation of various components from natural or synthetic mixtures. It has been one of the prime methods for isolating compounds from Traditional Chinese Medicines (TCM) and other comprehensive natural products. Although early CCC models produced a long-standing false image that CCC is a time-consuming technique, rapid and high-performance CCC devices and methods for high-throughput analysis of natural mixtures have been advanced. For instances, multi-channel CCC, dual CCC, elution-extrusion CCC, and solvent simplification protocols can provide high-throughput CCC analysis and produce high purity of compounds or large natural prod... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039222 Wed, 29 Sep 2010 23:00:00 +0100 4039222 http://www.medworm.com/index.php?rid=4039221&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883189%26dopt%3DAbstract Authors: Feng A, Tian B, Hu J, Zhou P Traditional Chinese medicines (TCMs) are generally mixtures of herbal plants or extracts which comprise hundreds of different constituents with widely difference in the content and physiochemical properties. In order to analyze bioactive compounds in TCMs and control the quality, a large number of analytical tools have been developed, among which capillary electrophoresis (CE) has become a powerful technique with increasing importance. Some formats of CE, including capillary zone electrophoresis, micellar electrokinetic chromatography, non-aqueous CE and capillary electrochromatography have been widely employed for the analysis of TCMs. The general characteristics of these formats are briefly described, and their applications to the analysis of TCM... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039221 Wed, 29 Sep 2010 23:00:00 +0100 4039221 http://www.medworm.com/index.php?rid=4039220&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883190%26dopt%3DAbstract Authors: Liang YZ, Xie PS, Chan K Chromatographic fingerprinting technique of traditional Chinese medicine (TCM) has proved to be a comprehensive strategy for assessing the intact quality of herbal medicine. In general, one could use the chromatographic techniques to obtain a relatively complete picture of herbal medicines, which are in common called chromatographic fingerprints of herbal medicines to represent the so-called phytoequivalence. Based on this, the features of chromatographic fingerprints of herbal medicines have been discussed in some detail. The technique based on chromatographic fingerprinting is essentially a kind of high-throughput and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs, some new ... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039220 Wed, 29 Sep 2010 23:00:00 +0100 4039220 http://www.medworm.com/index.php?rid=4039219&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883191%26dopt%3DAbstract Authors: Liu EH, Qi LW, Li K, Chu C, Li P Traditional Chinese medicines (TCMs) have been used for disease prevention and therapy in China for a long time and are becoming increasingly popular over the world. However, TCMs are complex mixtures and contain usually hundreds of chemically different constituents, which make the quality control of crude drugs and their medical preparations extremely difficult. Therefore, better analytical strategies to assure their efficacy, safety and consistency are in great demand. The present work provides an overview of the development of quality control for TCMs based on microscopic and molecular identification, quantitative and qualitative analysis, fingerprint, combination of fingerprint and multi-component quantification, as well as activity-integra... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039219 Wed, 29 Sep 2010 23:00:00 +0100 4039219 http://www.medworm.com/index.php?rid=4039218&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883192%26dopt%3DAbstract Authors: Yu F, Kong L, Zou H, Lei X Traditional Chinese medicines (TCMs), as an important component of natural medicines, still play an irreplaceable role in treatment of diseases because of their reliable clinical practice. However, the identification of the active compounds constitutes a bottleneck in the development of TCMs. Screening and analysis of active compounds is always a challenge in TCMs research. This review summarizes the present strategies for screening and analysis of bioactive compounds in TCMs based on molecular recognition, metabolism and omics. All the strategies were developed with the basic principles of meeting the TCMs characteristics. The recent progress about main biological fingerprinting methods, including microdialysis/CUF-HPLC, biochromatography, metabolic... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039218 Wed, 29 Sep 2010 23:00:00 +0100 4039218 http://www.medworm.com/index.php?rid=4039217&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883193%26dopt%3DAbstract Authors: Naoghare PK, Song JM At present, high-throughput screening (HTS) programs in drug discovery rely mainly on compound libraries from combinational chemistry. Similarly, natural flora has been used as a prominent origin for new and potent herbal drugs. Herbal medicines have been used worldwide for thousands of years to cure many diseases. As such, herbal secondary metabolites show a remarkable structural diversity that supplements chemically synthesized compound analogs in drug discovery screening. Unfortunately, there is often a considerable deterioration in the quality of herbal drugs in such screening programs as there are time-consuming manual processes involved in the isolation of active ingredients from the highly complex mixtures of herbal plant products. The quality and q... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039217 Wed, 29 Sep 2010 23:00:00 +0100 4039217 http://www.medworm.com/index.php?rid=4039216&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883194%26dopt%3DAbstract This article reviews the current and future researches on the enzyme inhibitors screening from TCM. PMID: 20883194 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039216 Wed, 29 Sep 2010 23:00:00 +0100 4039216 http://www.medworm.com/index.php?rid=4039215&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20883195%26dopt%3DAbstract Authors: Zhu Y, Zhang Z, Zhang M, Mais DE, Wang MW Throughout the centuries, traditional Chinese medicine has been a rich resource in the development of new drugs. Modern drug discovery, which relies increasingly on automated high-throughput screening and quick hit-to-lead development, however, is confronted with the challenges of the chemical complexity associated with natural products. New technologies for biological screening as well as library building are in great demand in order to meet the requirements. Here we review the developments in these techniques under the perspective of their applicability in natural product drug discovery. Methods in library building, component characterizing, biological evaluation, and other screening methods including NMR and X-ray diffraction are di... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=4039215 Wed, 29 Sep 2010 23:00:00 +0100 4039215 http://www.medworm.com/index.php?rid=3987690&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20849389%26dopt%3DAbstract Authors: Ozkan SA PMID: 20849389 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=3987690 Tue, 31 Aug 2010 23:00:00 +0100 3987690 http://www.medworm.com/index.php?rid=3881704&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712584%26dopt%3DAbstract Authors: Xiong X, Lu Y, Zhang L, Wang B, Zhao Y, Wang XJ, Huo X, Shen Y, Liang Z, Chen M Bone remodeling is tightly controlled by the actions of osteoblast and osteoclast. Impaired osteoblast proliferation and differentiation may disrupt the balance and lead to pathological symptom such as osteoporosis. To help understand the molecular mechanism of osteoblast proliferation, we performed a phenotype-driven high throughput screening with a random siRNA library, in search of novel genes that can accelerate murine preosteoblast MC3T3-E1 cell proliferation. Three siRNAs screened from the library were able to enhance MC3T3-E1 cell proliferation significantly. One of the proliferation-enhancing siRNAs (B7) was further subjected to expression profiling to pinpoint genes that putatively act dow... Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=3881704 Sun, 15 Aug 2010 23:00:00 +0100 3881704 http://www.medworm.com/index.php?rid=3776131&cid=s_37005_59_f&fid=37005&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20618146%26dopt%3DAbstract Authors: Ozkan SA PMID: 20618146 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening) Combinatorial Chemistry and High Throughput Screening journals http://www.medworm.com/rss/comments.php?id=3776131 Thu, 22 Jul 2010 08:09:06 +0100 3776131