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 'Prous Science - Molecule of the Month' source. Tue, 30 Mar 2010 16:17:06 +0100 http://www.medworm.com/index.php?rid=3219690&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D193 Post-transcriptional control mechanisms are all the regulatory events that take place after a messenger RNA (mRNA) molecule is copied from DNA (i.e., after the transcription process). These mechanisms include the decoding of the mRNA molecule so that a protein is synthesized, the determination of how efficiently an mRNA is utilized to make protein, and how long an mRNA lasts in a cell. All of these regulatory effects have a direct impact on how much protein is produced from each mRNA. Precise control of mRNA utilization is critical for many important functions, including the cell division cycle, the immune response, and the growth and repair of tissues. Small molecules that target post-transcriptional control to either up- or down-regulate protein production may have the potential to trea... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=3219690 Fri, 29 Jan 2010 15:52:09 +0100 3219690 http://www.medworm.com/index.php?rid=3138698&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D192 Cocaine is a substance of abuse whose primary sites of action in the brain have been identified as the monoamine neurotransmitter transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET). DAT, SERT and NET regulate the amount of dopamine, serotonin and norepinephrine available for signal transduction by removing excess monoamine from the synapse back to the presynaptic neuron. Cocaine is able to bind to these transporters and causes a blockade in neurotransmitter reuptake by the presynaptic neuron, thus prolonging neurotransmitter availability in the synaptic cleft. This leads to excessive activation of the postsynaptic neuron, as a consequence of increased binding of the neurotransmitters to their respective receptors, which is manifested as cocaine-induced reward/reinfo... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=3138698 Mon, 04 Jan 2010 15:50:49 +0100 3138698 http://www.medworm.com/index.php?rid=3039127&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D191 Hemodialysis-related uremic pruritus is characterized by severe systemic itching without inflammation of the skin. Its cause has not been elucidated, and it often does not respond to treatment by conventional antipruritic drugs, such as antihistamines. Pruritus is a common symptom seen in up to 90% of uremic patients, especially those with chronic renal failure requiring hemodialysis. The cause and mechanism of induction of pruritus are not known (Narita, I. et al., J Nephrol 2008, 21(2): 161). However, studies comparing hemodialysis patients with healthy subjects have provided evidence that an imbalance in the endogenous opioid system may be responsible for pruritus, with particular involvement of the kappa opioid system. Although existing kappa opioid receptor agonists lack morphine... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=3039127 Mon, 30 Nov 2009 16:19:29 +0100 3039127 http://www.medworm.com/index.php?rid=2942942&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D190 Tumor cells rely on the existence of a specialized vasculature for the oxygen and nutrients that they require in order to grow and survive. Targeting the tumor vasculature as a technique for inhibiting tumor growth was first attempted with angiogenesis inhibitors, a class of drugs that compromise the formation of new blood vessels. More recently a new class of drugs called vascular disrupting agents (VDAs) has been reported. Rather than preventing the formation of new blood vessels, VDAs target endothelial cells and pericytes in the already-established vascular network supporting the tumor. VDAs are designed to induce massive downstream tumor cell death in a tumor-specific manner, i.e. by shutting down the supporting vasculature. Two subtypes of VDAs have been described: ligand-directed VD... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2942942 Fri, 30 Oct 2009 15:46:28 +0100 2942942 http://www.medworm.com/index.php?rid=2850697&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D189 (EN:668987, EN:668959, EN:669086, EN:671307, EN:669516, EN:673657, EN:659629) The current pandemic of H1N1 influenza, the first cases of which were detected in Mexico in March 2009, has extended worldwide with astonishing speed, matched only by the speed of response by health authorities and the pharmaceutical industry. On April 27, slightly a month after the first cases were detected, the World Health Organization raised the pandemic alert level to phase 4, indicating confirmed human-to-human transmission of the virus resulting in community-level outbreaks. Just two days later, WHO raised the pandemic alert level to phase 5, thus acknowledging efficient community-level human-to-human transmission of the virus in at least two countries within a single WHO region. On June 11, the WHO raised... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2850697 Thu, 01 Oct 2009 18:14:02 +0100 2850697 http://www.medworm.com/index.php?rid=2751001&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D188 Bacillus anthracis, the organism that causes anthrax infections, was the first bacterium demonstrated to cause a disease. The use of anthrax as a biological weapon dates back to World War I, when the German army is believed to have injected horses, mules and cattle with anthrax toxin. In 1937 Japan initiated a biological warfare program, and the U.S. and U.K. followed suit half a decade later. The United States' biological weapons program was terminated in 1969, and in 1972 the Biological Weapons and Toxins Convention outlawed the development and stockpiling of biological weapons. Since that time, however, this class of weapon has remained in the shadows, primarily developed and stockpiled by underground terrorist groups in addition to certain “renegade” countries. In the 1990s the Jap... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2751001 Tue, 01 Sep 2009 13:25:21 +0100 2751001 http://www.medworm.com/index.php?rid=2660028&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D187 Xoma recently presented new results from a phase I clinical trial of XOMA-052, a novel antiinflammatory approach for the treatment of type 2 diabetes. XOMA-052 is a humanized monoclonal antibody (MAb) against interleukin-1beta (IL-1beta), the elevated expression of which has been correlated with damage to insulin-producing beta cells in patients with type 2 diabetes. In this trial, a single intravenous infusion of XOMA-052 (0.01, 0.03 or 0.1 mg/kg) or placebo was administered to individuals with inadequately controlled type 2 diabetes who were subsequently assessed for safety, pharmacokinetics and various diabetes and inflammation-related parameters for up to a period of 3 months. Treatment with XOMA-052 was well tolerated without the incidence of any serious adverse events. A reduction in... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2660028 Sat, 01 Aug 2009 12:00:41 +0100 2660028 http://www.medworm.com/index.php?rid=2555361&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D186 This study validates APT synthase as a target for tuberculosis (Diacon, A.H. et al., New Engl J Med 2009, 360(23): 2397). The second stage of the study, which will evaluate efficacy following 24 weeks of treatment, is currently ongoing and is actively recruiting patients with MDR-TB in South Africa, Peru, Latvia and Russia. Results from the second stage are expected to be available in 2010. In late June, Tibotec and the not-for-profit Global Alliance for TB Drug Development (TB Alliance) announced an agreement to collaborate and share their expertise and resources in order to speed the development of TMC-207, potentially the first TB drug with a new mechanism of action in 40 years. Under the terms of the agreement, Tibotec will continue to develop TMC-207 for the treatment of MDR-TB, and... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2555361 Tue, 30 Jun 2009 16:23:41 +0100 2555361 http://www.medworm.com/index.php?rid=2445934&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D185 Receptor activator of NF-kappaB ligand (RANKL) is a member of the tumor necrosis factor (TNF) family of cytokines that is produced by cells of osteoblastic lineage, and its cellular receptor RANK is present on the surface of hematopoietic osteoclast precursor cells as well as on mature osteoclasts. RANKL is now known to be the common and requisite factor intervening in osteoclast formation in response to all known catalysts. As such, the RANK/RANKL/osteoprotegerin pathway is essential for the process of osteoclastogenesis and modulates the differentiation, activation and survival of osteoclasts, thereby regulating bone resorption. Compounds acting on this pathway are being actively investigated for the treatment of osteoporosis (Integrity Disease Briefings: Osteoporosis [consulted May 28, ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2445934 Sun, 31 May 2009 04:20:29 +0100 2445934 http://www.medworm.com/index.php?rid=2379752&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D184 Malignant ascites is a condition characterized by the abnormal accumulation of fluid in the abdominal cavity. It is caused by an imbalance between plasma flow into and out of the blood and lymphatic vessels, and may develop in patients with cancer —primarily ovarian, endometrial, breast, colorectal, gastric and pancreatic cancers. Generally, the development of malignant ascites can be traced back to the settlement of metastasizing cancer cells in the abdominal cavity. The infiltrating cancer cells disrupt the normal regulation of fluid flow in the peritoneal cavity by simultaneously causing greater plasma inflow as well as reduced lymphatic outflow. Symptoms of malignant ascites include increasing abdominal girth, abdominal pain, anorexia, nausea and vomiting. Patients with malignant... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2379752 Thu, 30 Apr 2009 18:41:40 +0100 2379752 http://www.medworm.com/index.php?rid=2323718&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D183 Orexins (hypocretins) are a class of hypothalamic neuropeptides first described in the late 1990s. They have since been shown to regulate the sleep/wake cycle by maintaining wakefulness, as well as being involved in appetite regulation and energy homeostasis. Orexins A and B bind to two CNS receptors, designated orexin-1 and orexin-2. The cell bodies of orexin-producing neurons are restricted to the dorsal, lateral and posterior hypothalamus and its perifornical nucleus. Axonal projections of these cells are dense in the hypothalamus and extend to the limbic system, thalamus, substantia nigra, raphe, locus coeruleus, ventral tegmental area, medullary reticular formation, nucleus of the solitary tract and other brain stem regions. Orexin neurons have been shown in electrophysiological studi... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2323718 Sat, 11 Apr 2009 15:42:25 +0100 2323718 http://www.medworm.com/index.php?rid=2227664&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D182 (BAY-63-2521) is an oral soluble guanylate cyclase stimulator in phase III clinical development at Bayer Schering Pharma for the treatment of chronic thromboembolic pulmonary hypertension and for the treatment of pulmonary arterial hypertension (PAH). The compound stimulates sGC, which leads to the catalyzing of cyclic guanosine monophosphate (cGMP), resulting in the dilation of blood vessels, lowering of blood pressure and the mediation of tissue-protective effects. In February, Bayer Schering Pharma initiated two phase III clinical trials of riociguat: CHEST-1 (chronic thromboembolic pulmonary hypertension sGC stimulator trial) and PATENT-1 (pulmonary arterial hypertension sGC stimulator trial). CHEST-1 is a multicenter, double-blind, randomized, placebo-controlled trial in patients wi... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2227664 Mon, 02 Mar 2009 23:40:12 +0100 2227664 http://www.medworm.com/index.php?rid=2150916&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D181 In this study, 1,380 patients diagnosed with moderate to severe migraine according to International Headache Society (IHS) criteria were treated with telcagepant (150 or 300 mg), zolmitriptan (5 mg) or placebo. Five co-primary endpoints were evaluated at 2 hours postdosing: pain freedom, pain relief, absence of photophobia, absence of phonophobia and absence of nausea. Telcagepant was significantly more effective than placebo in terms of all five endpoints. Furthermore, while the efficacy of the CGRP antagonist was comparable to that of the zolmitriptan, telcagepant was associated with fewer adverse events (Ho, T.W. et al., Lancet 2008, 372(9656): 2115). Merck plans to file an NDA for telcagepant later this year in the U.S. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2150916 Mon, 02 Feb 2009 13:09:31 +0100 2150916 http://www.medworm.com/index.php?rid=2075237&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D180 The emergence of multidrug-resistant Gram-positive pathogens has created a need for newer antibacterial agents with improved efficacy. Researchers have focused on modifying the antibiotic vancomycin and other glycopeptides by adding hydrophobic substituents in order to improve activity, absorption, distribution, metabolism and excretion. Telavancin is one such novel antibiotic that was found to have multiple mechanisms of action, including inhibition of bacterial cell wall formation and disruption of cell membrane integrity. The agent showed potent activity in vitro and in vivo against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, among other bacterial species. Telavancin was also shown to have good pharmacokinetics and was effective in clinical t... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=2075237 Sat, 03 Jan 2009 15:06:08 +0100 2075237 http://www.medworm.com/index.php?rid=1996951&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D179 Tricyclic antidepressants, while effective in treating mild to severe forms of depression, are associated with an extensive tolerability profile, making them a nonviable option to many patients. The newer selective serotonin reuptake inhibitors (SSRIs) are better tolerated when compared with their tricyclic predecessors, and have recently become the most widely used antidepressant agents. However, problems with specific side effects (particularly affecting sexual function) have compromised treatment compliance in some patients. There is also evidence to suggest that while SSRIs are effective in mild to moderate forms of depression, they may not be as effective in patients exhibiting very severe forms of the disease. Therefore, research efforts are still being directed towards finding new a... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1996951 Sat, 29 Nov 2008 11:09:42 +0100 1996951 http://www.medworm.com/index.php?rid=1921291&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D178 Multiple sclerosis (MS) is one of the most common diseases of the central nervous system, affecting more than 2,500,000 people around the world. MS is the result of damage to myelin, a protective sheath surrounding nerve fibres of the central nervous system. When myelin is damaged, this interferes with messages between the brain and other parts of the body. Altered peptide ligands (APLs) are analogues of peptide determinants with one or more substitutions at the amino acid positions required for contact with the T cell receptor. APLs can act as either partial agonists or antagonists of the T cell receptor in question. In the case of multiple sclerosis, the peptide is an altered version of myelin basic protein (MBP), one of the most important proteins attacked by the immune system in MS. MP... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1921291 Fri, 31 Oct 2008 12:57:25 +0100 1921291 http://www.medworm.com/index.php?rid=1841387&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D177 In 1980, the World Health Organization declared that variola virus, the etiologic agent of smallpox, had been eradicated on a global level. However, two decades later concerns remain that this infectious agent, which has an alarmingly high morbidity and mortality rate, could be used as an agent of biological warfare. In recent years investigation into potential new vaccines and antiviral drugs for the treatment and prevention of smallpox virus infection has gained renewed strength, driven in part by support from the U.S. FDA and Centers for Disease Control and Prevention (CDC). Tecovirimat (ST-246), an inhibitor of orthopoxvirus egress from infected cells, is one promising agent to emerge from this new wave of research. The drug, an orally active inhibitor of core protein cysteine protei... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1841387 Wed, 01 Oct 2008 13:54:45 +0100 1841387 http://www.medworm.com/index.php?rid=1750498&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D176 (ISIS-301012) is a 20-mer antisense chimeric phosphorothiate oligonucleotide that selectively targets apolipoprotein B (apoB), a protein critical to the synthesis and transport of LDL and VLDL cholesterol, both involved in the development of heart disease. It is in phase III clinical trials at Isis Pharmaceuticals for the subcutaneous treatment of familial hypercholesterolemia. The compound is also in phase II clinical development for the treatment of hypercholesterolemia, and in phase II in combination with simvastatin for the treatment of atherosclerosis in patients with high cholesterol. In June 2006, mipomersen received orphan drug status from the FDA for the treatment of homozygous familial hypercholesterolemia. In 2008, the compound was licensed by Isis to Genzyme for worldwide deve... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1750498 Tue, 02 Sep 2008 12:22:47 +0100 1750498 http://www.medworm.com/index.php?rid=1671917&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D175 Hereditary angioedema (HAE) is an uncommon hereditary disorder that can cause sudden and severe attacks of nonpitting edema that may affect any external or mucosal surface including the face, arms, legs, hands, feet, genitalia, digestive track and airway. Although it is uncomfortable and cosmetically unacceptable, it is rarely dangerous. Severe urticaria or angioedema, however, may sometimes cause swelling of mucous membranes of the respiratory or gastrointestinal tracts, resulting in anaphylaxis or asphyxiation. The pathogenesis of HAE is due to a mutation in the gene encoding for the plasma protein C1 inhibitor. Treatments for hereditary angioedema include C1 inhibitor concentrate, attenuated androgens (danazol, oxandrolone) or fresh frozen plasma (Integrity® Disease Briefings: Urica... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1671917 Fri, 01 Aug 2008 12:28:04 +0100 1671917 http://www.medworm.com/index.php?rid=1554619&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D174 Deposition of amyloid beta (Abeta) peptide into plaques is one of the two hallmark features of Alzheimer's disease. These plaques, typically concentrated in the spaces between nerve cells in the brain parenchyma and cerebral blood vessel walls, are thought to impede nerve cell function and promote neuronal degeneration in Alzheimer's disease brains. According to current thinking, AD etiology is explained by the amyloid cascade hypothesis, whereby overproduction of Abeta protein, or alternatively the failure to clear this protein, leads to the accumulation of amyloid deposits and contributes to the formation of neurofibrillary tangles. These lesions are associated with neuronal cell death, which manifests as loss of memory. Thus strategies to prevent the formation, accumulation or cytotoxic... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1554619 Mon, 30 Jun 2008 11:05:43 +0100 1554619 http://www.medworm.com/index.php?rid=1478324&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D173 Thrombopoietin (TPO) is a glycoprotein hormone produced primarily by the liver that activates megakaryocytes in the bone marrow, causing them to differentiate and fragment into platelets. Under normal circumstances, the bloodstream platelet counts range from 150,000 to 400,000/mcl. However, under conditions of thrombocytopenia, platelet counts may drop below 50,000/mcl. Under these circumstances, patients are predisposed to bleeding, particularly at mucous membranes, and in some cases bleeding may become severe enough to require treatment. Thrombocytopenia is commonly associated with cancer chemotherapy and a number of other conditions, including AIDS, myelodysplastic syndrome, idiopathic thrombocytopenic purpura and chronic liver disease. The only treatment currently available for severe ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1478324 Fri, 30 May 2008 16:17:39 +0100 1478324 http://www.medworm.com/index.php?rid=1415084&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D172 Cathepsin K is a cysteine protease that is selectively and highly expressed by osteoclasts and secreted into the extracellular compartment, where it cleaves important bone matrix proteins, acting as the principal effector of bone degradation during the process of bone resorption. Activated cathepsin K degrades various bone matrix components including type I collagen, osteopontin and osteonectin. It is an attractive target for modulation in osteoporosis and other disorders caused by excessive bone resorption, because while it is expressed at high levels in bone, it is present at extremely low levels in the heart, liver, lung and other tissues. At the present time several cathepsin K inhibitors are under active development for the treatment of osteoporosis, including Merck & Co.’s odanacat... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1415084 Fri, 02 May 2008 08:56:02 +0100 1415084 http://www.medworm.com/index.php?rid=1338311&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D171 Cryopyrin-Associated Periodic Syndromes (CAPS) are a recently identified group of rare, inherited auto-inflammatory disorders characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise or other unknown stimuli. Three related conditions fall under the classification of CAPS: Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). The incidence of CAPS has been reported to be approximately 1 in 1,000,000 people in the United States. CAPS are generally caused by mutations in the NLRP-3 (previously known as CIAS1) gene and resultan... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1338311 Mon, 31 Mar 2008 20:27:32 +0100 1338311 http://www.medworm.com/index.php?rid=1268728&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D169 In this study, patients responding to ustekinumab at week 40 were randomized to either continue treatment or switch to placebo. At week 52, 87% and 91% of patients receiving ustekinumab 45 and 90 mg, respectively, maintained a PASI 75 response, compared to 64% and 62% of placebo-treated patients. Long-term maintenance therapy was generally well tolerated, with 46% and 49% of patients in the 45 and 90 mg dose groups, respectively, experiencing at least one adverse event after randomization at week 40, compared to 56% and 48% of patients switched to placebo (Gordon, K.B. et al., J Am Acad Dermatol 2008, 58(2, Suppl. 2): Abst P2620). Centocor and Jassen-Cilag have filed for regulatory approval of ustekinumab in the U.S. and European Union, respectively, for th... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1268728 Fri, 29 Feb 2008 21:38:53 +0100 1268728 http://www.medworm.com/index.php?rid=1192972&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D168 Despite the availability of several approved drugs for the treatment of human immunodeficiency virus (HIV) infection, the limited effectiveness of current antiretroviral regimens, mainly due to the emergence of resistance, makes the development of new agents necessary. Several novel compounds are being added to existing classes, but the discovery and development of newer classes of antiretroviral drugs, such as HIV entry inhibitors, represents a significant advance in the treatment of AIDS and HIV. HIV enters the host cell by a sequential process that requires engagement with CD4 followed by binding to a coreceptor: either the chemokine CCR5 receptor (R5 strains) or CXCR4 (RX strains). The chemokine CCR5 receptor is a G-protein-coupled, 7-transmembrane receptor expressed on monocytes, mac... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1192972 Fri, 01 Feb 2008 09:28:58 +0100 1192972 http://www.medworm.com/index.php?rid=1122583&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D167 (GX15-070) is a small-molecule indole bipyrrole drug compound and pan-Bcl-2 family inhibitor being developed at Gemin X Biotechnologies for the treatment of cancer. Recently published studies have confirmed the mechanism of action of the compound, demonstrating that it specifically disrupts the survival of cancer cells as a result of inhibiting the Bcl-2 pro-survival protein Mcl-1. Elevated expression of members of the Bcl-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells, and obatoclax overcomes Bcl-2 pro-survival proteins' resistance to the pro-apoptotic proteins BAX and BAK. The anti-apoptotic protein Mcl-1 plays a particularly central role in conferring cancer cell resistance in certain instances, and obatoclax potently interferes with the direct int... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1122583 Mon, 31 Dec 2007 14:15:33 +0100 1122583 http://www.medworm.com/index.php?rid=1061263&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D166 Synta Pharmaceuticals' elesclomol (STA-4783), a first-in-class small-molecule oxidative stress inducer, has been selected as the Molecule of the Month. Elesclomol induces an oxidative stress response in cancer cells by inducing heat shock protein 70 (Hsp70), thereby inducing apoptosis and enhancing the activity of certain anticancer agents such as paclitaxel. In October, Synta signed a global collaboration agreement with GlaxoSmithKline for the joint development and commercialization of elesclomol. Under the terms of the agreement, the companies will share responsibility for development and commercialization of elesclomol in the U.S. and GSK will have exclusive responsibility for development and commercialization of the product outside the U.S. In addition, Synta will also be eligible to r... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=1061263 Fri, 30 Nov 2007 14:45:21 +0100 1061263 http://www.medworm.com/index.php?rid=993444&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D165 Sodium-dependent glucose transport proteins (SGLTs) play a key role in maintaining glucose homeostasis in the human body. SGLTs are found in the intestine (SGLT1) and the kidney (SGLT1 and SGLT2). Renal SGLT reabsorbs glucose from the renal filtrate, thus preventing loss of glucose in urine. Renal SGLTs are found in the pars convoluta of the nephron's proximal tubule. SGLTs use the energy from a positive sodium gradient to transport glucose across the membrane. SGLT2 has a 1:1 ratio of sodium-glucose transport. SGLT1 works similarly but has a 2:1 ratio of sodium-glucose transport. SGLT2 accounts for 98% of renal glucose reabsorption, whereas SGLT1 accounts for the remaining 2%. Transcellular glucose transport is facilitated by the basolateral membrane glucose transporters GLUT2 and... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=993444 Wed, 31 Oct 2007 14:00:30 +0100 993444 http://www.medworm.com/index.php?rid=916239&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D164 , a reversal agent used during general anesthesia, is the first selective relaxant binding agent (SRBA), a drug-specific cyclodextrin that is specifically designed to reverse the effects of the muscle relaxant rocuronium bromide (Esmeron®/Zemuron®) when the latter is used as a component of general anesthesia during surgical procedures. Current reversal agents can only be administered when muscle relaxation is starting to wear off naturally; however, sugammadex can achieve reversal following rocuronium bromide administration within three minutes, regardless of the depth of block. Furthermore, in studies to date, sugammadex has shown less adverse effects than the currently available agents. Sugammadex encapsulates the muscle relaxant and forms a very tight, water-soluble host-guest c... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=916239 Mon, 01 Oct 2007 13:28:17 +0100 916239 http://www.medworm.com/index.php?rid=855420&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D43 Marimastat is an orally active, second-generation matrix metalloproteinase inhibitor (MMPI) from British Biotech that is currently undergoing extensive phase II evaluation in several countries, including the U.S. and the U.K., for the treatment of patients with advanced solid tumors, such as colorectal, ovarian, pancreatic and prostatic tumors. Unlike conventional anticancer agents, MMPIs are not cytotoxic, but rather act to prevent the spread or progression of cancers. They are thus expected to have little effect on normal tissue, and are intended for use as maintenance therapy following chemotherapy or surgery, or for poorly treated cancers. Results presented this week have confirmed a dose-dependent effect on cancer antigen levels and shown that this effect is correlated with clinical o... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855420 Mon, 10 Sep 2007 01:39:34 +0100 855420 http://www.medworm.com/index.php?rid=855419&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D44 Warner-Lambert is filing regulatory submissions for its HMG-CoA reductase inhibitor, atorvastatin, this month in the United States, France, the United Kingdom, Australia, New Zealand, Switzerland and South Africa, and filings are expected soon in Germany and Canada. Atorvastatin reportedly represents an advance over existing statin compounds as a lipid regulator. It has been shown particularly effective at lowering total cholesterol and LDL-cholesterol, where reductions on the order of 60% have been demonstrated. The first clinical data on the pharmacokinetics and safety of Discovery Therapeutics' N-0923 transdermal patch for the treatment of Parkinson's disease are being presented this month at the Fourth International Congress of Movement Disorders in Vienna. The company has also rep... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855419 Mon, 10 Sep 2007 01:39:34 +0100 855419 http://www.medworm.com/index.php?rid=855418&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D45 Ciba has identified a lead compound, CGP-52608, from a series of thiazolidinediones that are highly effective in suppressing chronic inflammation and joint destruction in the rat adjuvant arthritis model. CGP-52608 was found to specifically activate the retinoid Z receptor (RZR)/retinoic acid receptor-related orphan receptor alpha (ROR alpha) at low concentrations, and structure-activity studies with analogues demonstrated a marked correlation between RZR/ROR alpha activation and antiarthritic activity. This receptor is a member of the superfamily of inducible transcription factors, and researchers at Ciba recently identified melatonin as the natural ligand. Thus, the receptor appears to be a promising target for the treatment of rheumatoid arthritis and other autoimmune diseases... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855418 Mon, 10 Sep 2007 01:39:34 +0100 855418 http://www.medworm.com/index.php?rid=855417&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D46 (AGN-190168; Allergan) is the first of a new generation of receptor-selective retinoids specifically designed for the topical treatment of mild to moderate plaque psoriasis. Data from a large-scale, controlled clinical trial have demonstrated that tazarotene in a topical gel formulation is safe and efficacious, and that it continues to show therapeutic effects 12 weeks posttreatment (Drake, L. et al. Clin Dermatol 2000 (May 28-31, Vancouver) 1996, Abst. 352; see also abstracts 351 and 353). (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855417 Mon, 10 Sep 2007 01:39:34 +0100 855417 http://www.medworm.com/index.php?rid=855416&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D47 , an analog of the natural human hormone amylin, is in development by Amylin and Johnson & Johnson for improving glucose control in patients with type 1 or 2 diabetes who use insulin, thereby reducing the risk of diabetic complications. Results from a recent phase II trial in patients with type 2 diabetes who self-administered the drug for one month demonstrated its ability to significantly reduce blood glucose concentrations without causing hypoglycemia, and reaffirmed its good short-term safety. Six phase III trials are in progress in the U.S. and Europe (Amylin News Release). (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855416 Mon, 10 Sep 2007 01:39:34 +0100 855416 http://www.medworm.com/index.php?rid=855415&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D48 The Royal Swedish Academy of Sciences has awarded the 1996 Nobel Prize in Chemistry jointly to Professor Robert F. Curl, Jr. and Professor Richard E. Smalley, both of Rice University (Houston, TX, U.S.A.) and Professor Sir Harold W. Kroto of the University of Sussex (Brighton, U.K.), for their discovery of the fullerenes. These compounds, new forms of the element carbon, were discovered by the trio in 1985 and first published in the scientific journal Nature in November of the same year. Fullerenes are formed when vaporized carbon condenses in an atmosphere of inert gas. The gaseous carbon is obtained by methods such as directing an intense pulse of laser light at a carbon surface. The released carbon atoms are mixed with a stream of helium gas and combine to form clusters of a few up to h... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855415 Mon, 10 Sep 2007 01:39:34 +0100 855415 http://www.medworm.com/index.php?rid=855414&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D49 is a new thienopyridine antiplatelet agent discovered by Sanofi that prevents blood clot formation inside an atherosclerotic artery by inhibiting platelet activation and aggregation. Sanofi recently announced the results of the large, international CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) trial at the 69th Scientific Sessions of the American Heart Association, showing a significant reduction in such events compared to aspirin, as well as good safety. The CAPRIE study demonstrated that treatment with clopidogrel provided an overall relative risk reduction for ischemic stroke, myocardial infarction (MI, or heart attack) or vascular death of 8.7% among 9,599 patients treated with this drug compared with the 9,586 patients treated with aspirin (p = 0.043). Cl... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855414 Mon, 10 Sep 2007 01:39:34 +0100 855414 http://www.medworm.com/index.php?rid=855413&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D50 Interim results from a phase I/II clinical trial assessing Ligand Pharmaceuticals' TargretinTM (LGD-1069) topical gel formulation in 30 patients with cutaneous T cell lymphoma (CTCL) were reported at the American Society of Hematology annual meeting in Orlando, Florida, in early December 1996. The trial was designed to assess the safety and efficacy of escalating doses (beginning as 0.1% gel q.d., escalated every two weeks as tolerated to 0.1% b.i.d., 0.5% q.d., 0.5% b.i.d., 1.0% q.d. and 1.0% b.i.d.) of the product in patients with stage I/IIa CTCL. A retinoid X receptor (RXR) receptor-selective retinoid, Targretin was generally well tolerated, with some retinoid erythema and irritation reported, and responses of at least four weeks in duration were reported by 11 out of 27 evaluable pati... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855413 Mon, 10 Sep 2007 01:39:34 +0100 855413 http://www.medworm.com/index.php?rid=855412&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D51 is a selective, orally active inhibitor of 5- lipoxygenase (5-LO) from Abbott, proven to exert antiinflammatory and antiallergic effects in animal models and humans. The FDA cleared zileuton (Zyflo[TM]) for the prevention and chronic treatment of asthma in patients at least 12 years of age in December, and Abbott launched it on January 28th (Abbott News Release). (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855412 Mon, 10 Sep 2007 01:39:34 +0100 855412 http://www.medworm.com/index.php?rid=855411&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D52 (Aricept[TM]) is a reversible acetylcholinesterase inhibitor discovered by Eisai, available as of this week in the U.S. for the treatment of mild to moderate symptoms of Alzheimer's disease. It has also been submitted for approval in the U.K. and will be comarketed/copromoted in these two countries by Eisai and Pfizer. Pfizer also holds codevelopment rights in Japan and certain other European countries, and exclusive rights in Canada and Australia. Bracco has been granted copromotion rights to the drug for Italy. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855411 Mon, 10 Sep 2007 01:39:34 +0100 855411 http://www.medworm.com/index.php?rid=855410&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D53 Researchers at Gilead Sciences, the University of California, Berkeley, and the Australian National University have discovered and developed a novel class of carbocyclic compounds for the treatment and prevention of influenza (flu) --the neuraminidase inhibitors-- which block an enzyme necessary for the replication of the virus. The lead compound, GS-4104, exhibits potent, broad-spectrum activity against multiple strains of influenza A and B, is orally active and appears to be devoid of side effects. Gilead and Roche are collaborating on the development and worldwide commercialization of GS-4104 for both the prevention and treatment of influenza infections. This lead candidate was identified only a year ago and is expected to enter trials in humans in the first half of 1997. (Source: Prous... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855410 Mon, 10 Sep 2007 01:39:34 +0100 855410 http://www.medworm.com/index.php?rid=855409&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D54 (BMS-180194) was identified by Bristol-Myers Squibb as the active enantiomer of BHCG (SQ-33054), a cyclobutane nucleoside analogue with antiviral activity against herpesviruses and HIV. Lobucavir has a broad spectrum of activity against herpesviruses, including aciclovir-resistant herpes simplex virus (HSV) and ganciclovir-resistant cytomegalovirus (CMV), and hepatitis B. It has good oral bioavailability and is also effective when given topically. Results from clinical studies have demonstrated its safety and efficacy against CMV infection in HIV-infected patients after oral administration. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855409 Mon, 10 Sep 2007 01:39:34 +0100 855409 http://www.medworm.com/index.php?rid=855408&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D55 The epothilones are a new class of natural cytotoxic agents originally isolated from a cultured strain of the myxobacterium Sorangium cellulosum. These compounds work in the same way as paclitaxel (Taxol) to inhibit cancer cell proliferation, promoting microtubule assembly and stabilization, but results from in vitro studies indicate that they are also active against paclitaxel- resistant cancer cell lines. Although several syntheses of epothilone A and epothilone B have been reported, the first solid-phase synthesis of epothilone A and the total synthesis of epothilone B, as well as the synthesis of epothilone analogues, have now been reported by investigators at The Scripps Research Institute in a recent issue of the journal Nature (Nicolau, K.C. et al. Nature 1997, 387(6630): 268... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855408 Mon, 10 Sep 2007 01:39:34 +0100 855408 http://www.medworm.com/index.php?rid=855407&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D56 At the 4th International Symposium on Osteoporosis Research Advances and Clinical Applications, held in Washington, D.C., U.S.A., June 4-7, 1997, researchers from Eli Lilly and Co. presented encouraging results from a phase III trial of raloxifene hydrochloride (LY-139481), a selective estrogen receptor modulator (SERM), as an alternative to hormone replacement therapy in the prevention of postmenopausal health risks, including osteoporosis. The compound increased bone mineral density, an indicator of risk for fracture, by 2-3% compared with placebo at all skeletal sites measured (hip, spine and total body). The increases in bone mineral density, 1-2% above baseline values, were statistically significant at 12 months and remained so at 24 months. The effects of raloxifene in preventing ske... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855407 Mon, 10 Sep 2007 01:39:34 +0100 855407 http://www.medworm.com/index.php?rid=855406&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D57 VX-710 is a new chemosensitizing agent under development by Vertex and its Canadian partner BioChem Therapeutic that is designed to restore the tumor-killing activity of chemotherapeutic agents in patients with cancer complicated by multidrug resistance (MDR). The compound reverses MDR by blocking both the P-glycoprotein (MDR1) and multidrug resistance-associated protein (MRP) mechanisms. In a phase I/II trial in patients with solid tumors, treatment with VX-710 and paclitaxel was well tolerated and the coadministration of VX-710 resulted in a significant paclitaxel-sparing effect, allowing the use of significantly lower paclitaxel doses to acheive and maintain blood levels comparable to those when the chemotherapeutic is given alone. VX-710 is presently undergoing phase II evaluat... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855406 Mon, 10 Sep 2007 01:39:34 +0100 855406 http://www.medworm.com/index.php?rid=855405&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D58 A is a bioengineered drug designed to be administered as a single intravenous injection over 5-10 seconds, dissolving clots that cause heart attacks without interfering with other clotting factors. Results from two new phase II studies on TNK-tPA were presented at the 19th Congress of the European Society of Cardiology, held in Stockholm, Sweden, August 24-28, 1997. TNK-tPA was found to have a comparable efficacy and safety profile to the 90-minute infusion of tissue plasminogen activator (tPA), the current standard treatment for heart attacks. The two phase II studies were conducted in parallel to evaluate the efficacy and safety of TNK-tPA at various doses in patients with heart attacks. The TIMI (Thrombolysis in Myocardial Infarction) 10B trial assessed the efficacy of TNK-tPA compare... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855405 Mon, 10 Sep 2007 01:39:34 +0100 855405 http://www.medworm.com/index.php?rid=855404&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D59 (DMP-266, Sustiva[TM]) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) from DuPont Merck which is undergoing extensive evaluation in combination with other antiretroviral agents and is currently in phase III trials for the treatment of HIV infection and AIDS. In phase II trials, significant suppression of HIV RNA was observed after monotherapy, and combination therapy with indinavir sulfate (Crixivan; Merck & Co.) reduced viral load to below the level of detection in a high percentage of patients and increased CD4 cell counts. Efavirenz has been detected in cerebrospinal fluid, is active against certain mutant variants of HIV-1 associated with NNRTI resistance, and is generally well tolerated. Additional studies are in progress or planned to evaluate its efficacy and safet... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855404 Mon, 10 Sep 2007 01:39:34 +0100 855404 http://www.medworm.com/index.php?rid=855403&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D60 HMR-3647 (RU-66647) is a new ketolide antibacterial agent in development by Hoechst Marion Roussel which has undergone extensive evaluation in vitro and in vivo. A number of in vitro studies were presented recently at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy in Toronto, demonstrating its potent and broad-spectrum activity. HMR-3647 displays antipneumococcal activity (including penicillin-resistant strains), excellent activity against respiratory pathogens, activity against vancomycin-resistant enterococci, as well as potential in the treatment of sexually transmitted and pelvic inflammatory infections, skin and soft tissue infections, staph infections, anaerobic infections and toxoplasmosis. The compound also possesses good activity in murine infection mode... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855403 Mon, 10 Sep 2007 01:39:34 +0100 855403 http://www.medworm.com/index.php?rid=855402&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D61 A new oral treatment for type II diabetes is being fast-tracked by the FDA and was recently recommended for approval for the treatment of type II diabetics not satisfactorily controlled by diet and exercise alone. Repaglinide (Prandin[TM]; NovoNorm[R] outside the U.S.) is the first in a new class of short- and fast-acting insulin release-promoting agents which is designed to regulate postprandial glucose loads. The nonsulfonylurea compound was codeveloped by Novo Nordisk and Boehringer Ingelheim, and the former holds worldwide marketing rights. Novo Nordisk has also filed for approval in the E.U., Norway, Switzerland and Canada. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855402 Mon, 10 Sep 2007 01:39:34 +0100 855402 http://www.medworm.com/index.php?rid=855401&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D62 The FDA recently approved Regranex® Gel (0.01%) as the first biologic for the treatment of diabetic foot ulcers. The active ingredient in Regranex® is becaplermin, a genetically engineered platelet-derived growth factor (rhPDGF-BB) developed and manufactured by Chiron. It mimics the effects of natural PDGF, stimulating the migration of cells to the ulcer site and thereby promoting the growth of new tissue. The gel will be marketed by Ortho-McNeil. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855401 Mon, 10 Sep 2007 01:39:34 +0100 855401 http://www.medworm.com/index.php?rid=855400&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D63 Endothelin (ET) has been implicated in a number of disorders, such as congestive heart failure and cerebral vasospasm following subarachnoid hemorrhage (SAH), and a potent ETA receptor antagonist suitable for parenteral administration appears to be of special interest in cerebral vasospasm. Unfortunately, endothelin antagonists have not yet fulfulled their promise as potential therapeutic agents for a variety of reasons, including low potency and low water solubility. Roche's Ro-61-1790, a follow-up compound to bosentan, the first ET antagonist to be tested in the clinic, belongs to a new generation of trifunctionalized heteroarylsulfonamide pyrimidine ET antagonists with high water solubility and high affinity and selectivity for the ETA receptor subtype. This compound produced... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855400 Mon, 10 Sep 2007 01:39:34 +0100 855400 http://www.medworm.com/index.php?rid=855399&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D65 February's 'Molecule of the Month' is not a molecule at all, but a manufactured living human skin equivalent developed by Organogenesis. Apligraf TM features both an epidermis and a dermis: the upper layer is comprised of living human epidermal cells (keratinocytes) and the lower layer of living human dermal cells (fibroblasts) in an organized dermal matrix. The skin equivalent thus takes as a graft and directly contributes to the wound-healing process by interacting with the wound bed. Apligraf TM is organized using Organogenesis' proprietary organotypic culturing technology which enables the cells to reproduce their natural three-dimensional arrangement, and thus can be handled like skin. The cells used in Apligraf TM come from infant foreskin, a readily available source o... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855399 Mon, 10 Sep 2007 01:39:34 +0100 855399 http://www.medworm.com/index.php?rid=855398&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D66 A novel genetically engineered product developed by Immunex in collaboration with the Wyeth-Ayerst division of American Home Products has recently been designated a "fast track product" for the treatment of advanced rheumatoid arthritis by the FDA, meaning that the agency will help expedite the development and review of the product. EnbrelTM (also referred to as TNF receptor, TNFR and TNFR:Fc) binds to and inhibits the activity of the proinflammatory cytokine TNF, thereby blocking the inflammatory response associated with rheumatoid arthritis. Clinical trials in patients with active rheumatoid arthritis, including those failing disease-modifying antirheumatic drugs (DMARDs), treated for up to six months with EnbrelTM have demonstrated significant improvement in swollen and tender joints an... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855398 Mon, 10 Sep 2007 01:39:34 +0100 855398 http://www.medworm.com/index.php?rid=855397&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D67 A new synthetic analogue of 1,25-dihydroxyvitamin D3 that retains the suppressive effect on parathyroid hormone (PTH) but shows minimal effects on calcium and phosphate metabolism was recently approved by the FDA for use in the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. Abbott's paricalcitol is the first vitamin D analogue to be approved for this indication. The company plans to introduce the product as Zemplar(TM) by the end of May. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855397 Mon, 10 Sep 2007 01:39:34 +0100 855397 http://www.medworm.com/index.php?rid=855396&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D68 Earlier this month, the FDA granted accelerated approval for a novel antitumor agent from Roche. Capecitabine belongs to a new class of drugs known as fluoropyrimidine carbamates that are activated mainly at the tumor site rather than in normal tissues. As the compound is largely inactive until it reaches the tumor site, its administration is associated with minimal serious side effects such as hair loss and bone marrow depression. Known as Xeloda™, it is the first oral anticancer drug approved for patients with metastatic breast cancer resistant to standard chemotherapy with paclitaxel and anthracycline-containing regimens. Roche has also applied for expedited review in the European Union and Nippon Roche is conducting phase II trials in Japan. (Source: Prous Science - Molecule of t... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855396 Mon, 10 Sep 2007 01:39:34 +0100 855396 http://www.medworm.com/index.php?rid=855395&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D69 Recombinant humanized anti-p185c-erbB2 (HER2) monoclonal antibody The first monoclonal antibody targeted at metastatic breast cancer is now under review at the FDA. Designated a fast track product by the agency, Genentech's trastuzumab (HerceptinTM) is a humanized anti-HER2 monoclonal antibody designed for the treatment of women with metastatic breast cancer whose tumors overexpress the growth factor receptor HER2. HER2 overexpression occurs in up to 30% of patients with breast cancer and is associated with an especially aggressive form of the disease characterized by more rapid disease progression and shortened survival. The recently submitted BLA was based on results from two phase III clinical trials, which were presented at the May ASCO (American Society of Clinical Oncology) meeting. ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855395 Mon, 10 Sep 2007 01:39:34 +0100 855395 http://www.medworm.com/index.php?rid=855394&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D70 In June 1998 Glaxo Wellcome submitted an NDA for its anti-HIV drug abacavir succinate (Ziagen™, formerly 1592U889) to the FDA seeking approval for both pediatric and adult dosage forms. Abacavir is a nucleoside reverse transcriptase inhibitor that appears to have superior antiviral activity compared to other drugs in this class. Ziagen™ has been designated a fast track product by the FDA. The company also submitted abacavir for approval in the European Union. Almost 8,000 HIV-infected patients have been treated with abacavir and the company has submitted comprehensive data including various patient opulations and various combinations. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855394 Mon, 10 Sep 2007 01:39:34 +0100 855394 http://www.medworm.com/index.php?rid=855393&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D71 Following its meeting on August 7, 1998, the FDA's Arthritis Advisory Committee unanimously recommended the approval of Hoechst Marion Roussel's arthritis drug Arava(TM) (leflunomide), granted priority review status by the FDA. Once final approval is received, leflunomide will be the first new disease-modifying agent specifically designed for the treatment of rheumatoid arthritis. The recommendation is for relief of the signs and symptoms of arthritis, as well as retardation of the structural damage associated with the disease. Leflunomide has a novel mechanism of action: it acts by inhibiting the enzyme dihydroorotate dehydrogenase (DHODH), thus slowing the proliferation of the activated lymphocytes that are linked to the pathophysiology of rheumatoid arthritis. In clinical stud... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855393 Mon, 10 Sep 2007 01:39:34 +0100 855393 http://www.medworm.com/index.php?rid=855392&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D72 New data on the characteristics of moxifloxacin were presented at the 38th Interscience Congress of Antimicrobial Agents and Chemotherapy (ICAAC) in San Diego while key findings from the past two years of research were also highlighted. Moxifloxacin, an 8-methoxyquinolone, has potent bactericidal activity against Gram-positive, Gram-negative and atypical pathogens. In vitro testing has confirmed moxifloxacin to be one of the most active quinolones against bacteria already resistant to penicillins and macrolides, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Mycobacterium tuberculosis. Additionally, moxifloxacin exhibits activity against methicillin-resistant Staphylococcus aureus. Research presented to date found that the oral formulatio... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855392 Mon, 10 Sep 2007 01:39:34 +0100 855392 http://www.medworm.com/index.php?rid=855391&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D73 Based on promising activity displayed in vitro and in clinical studies to date, SmithKline Beecham has initiated phase III clinical testing of SB-265805 (LB-20304a), a broad-spectrum oral fluoroquinolone with excellent antibacterial activity against key respiratory pathogens, including strains resistant to existing therapies. SmithKline Beecham obtained worldwide development and commercialization rights to SB-265805 from its originator, LG Chemical, and is targeting the compound for the treatment of community-acquired infections. SB-265805 was featured in a total of 20 abstracts and poster presentations at the recent 38th Interscience Conference Antimicrobial Agents & Chemotherapy (Sept 24-27, San Diego). (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855391 Mon, 10 Sep 2007 01:39:34 +0100 855391 http://www.medworm.com/index.php?rid=855390&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D74 (MK-966; VioxxTM) is a COX-2 inhibitor from Merck & Co. which has been studied extensively in patients with rheumatoid arthritis and osteoarthritis, as well as other painful conditions such as dental pain and menstrual cramps; future studies are planned in Alzheimer's disease and colon cancer. MK-966 has an excellent profile of antiinflammatory efficacy and a low propensity to cause side effects, especially gastrointestinal side effects commonly seen with NSAIDs. Merck & Co. plans to make the first regulatory filings later this year. Although no chemical structure was officially associated with the name MK-966 until the 9th International Conference of the Inflammation Research Association (November 1-5, Hershey) 1998, Prous Science first identified this compound in the patent lit... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855390 Mon, 10 Sep 2007 01:39:34 +0100 855390 http://www.medworm.com/index.php?rid=855389&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D75 The matrix metalloproteinase (MMP-2, MMP-8 and MMP-9) inhibitor and antiangiogenic compound Bay-12-9566 (Bayer) has been studied extensively in preclinical and clinical studies for the treatment of cancer, as reported in depth at several major meetings this year. In vivo in models of B16 murine melanoma and Lewis lung carcinoma, Bay-12-9566 produced approximately 50-60% inhibition of the growth of these fast-growing tumors following oral administration. Bay-12-9566 has been shown in laboratory tests to selectively inhibit those MMPs believed to be involved in the spread of new tumor growth, thereby keeping tumors in check indefinitely. Furthermore, the agent does not affect other MMPs that may be important in the functioning of normal tissues Toxicity studies showed that the compound i... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855389 Mon, 10 Sep 2007 01:39:34 +0100 855389 http://www.medworm.com/index.php?rid=855388&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D76 Ciba Vision, the eye-care unit of Novartis, and QLT PhotoTherapeutics have announced positive interim results from a phase III trial evaluating verteporfin (Visudyne[TM]) for the preservation of vision in patients with the wet form of age-related macular degeneration (AMD). The findings are based on an initial 12-month analysis of pivotal 24-month studies using verteporfin in photodynamic therapy of AMD. Results of the TAP (Treatment of AMD with Photodynamic therapy) investigation, which comprises two randomized, double-blind, placebo-controlled studies involving 609 patients at 22 European and North American centers, showed that patients treated with verteporfin were more likely to have stable vision or improved vision as compared to patients treated with placebo at 12-month follow-up.... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855388 Mon, 10 Sep 2007 01:39:34 +0100 855388 http://www.medworm.com/index.php?rid=855387&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D77 Vanguard Medica has submitted an NDA for frovatriptan (VML-251, formerly SB-209509; MiguardTM) 2.5 mg tablets to the U.S. FDA for the acute treatment of migraine. During an extensive clinical program, frovatriptan, a 5-HT1B/1D agonist, has been studied in trials involving more than 4,500 patients, including five placebo-controlled studies. The results of the phase III studies will be presented at major medical meetings and in neurology journals over the coming year. Vanguard has an exclusive worldwide license to commercialize frovatriptan in return for payment of a royalty on net sales to SmithKline Beecham, the compound's originator. Elan obtained exclusive North American sales and distribution rights to frovatriptan during the second half of 1998. Vanguard will be responsible ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855387 Mon, 10 Sep 2007 01:39:34 +0100 855387 http://www.medworm.com/index.php?rid=855386&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D78 Recombinant fusion protein in which the receptor-binding domain of native diphtheria toxin (DT) has been replaced with the polypeptide hormone IL-2. It consists of amino acid residues 2-133 of human IL-2 joined in correct translational reading frame to Ala389 of DT. The fusion protein binds to the high-affinity form of the IL-2 receptor and is internalized by receptor-mediated endocytosis. The FDA granted approval for Ontak(TM) (denileukin diftitox, DAB389IL-2) on February 5, 1999 for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor. Denileukin diftitox is produced by genetically fusing protein from the diphtheria toxin to IL-2, a naturally occurring immune system protein. Thi... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855386 Mon, 10 Sep 2007 01:39:34 +0100 855386 http://www.medworm.com/index.php?rid=855385&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D79 , a dual vasopeptidase (neutral endopeptidase and ACE) inhibitor from Bristol-Myers Squibb, is being evaluated extensively in clinical trials for the treatment of congestive heart failure and hypertension. Several studies have been reported at recent congresses –most recently at the 48th Annual Scientific Sessions of the American College of Cardiology– demonstrating the safety and efficacy of omapatrilat in healthy volunteers and in patients treated for periods of up to three months. The superior blood pressure-lowering activity reported for omapatrilat in healthy volunteers, as well as its sustained efficacy in reducing the combined incidence of death, hospitalization or cointervention for heart failure in patients with CHF, has been attributed to the dual inhibition of two... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855385 Mon, 10 Sep 2007 01:39:34 +0100 855385 http://www.medworm.com/index.php?rid=855384&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D80 The U.S. FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously April 22, 1999, to approve SmithKline Beecham's Avandia (rosiglitazone maleate, BRL-49653) for the treatment of type II diabetes as both monotherapy and in combination with metformin. Rosiglitazone is a new-generation thiazolidinedione that directly targets insulin resistance, an underlying cause of type II diabetes. The recommendation was based on clinical trials involving more than 5,000 patients with the disease, demonstrating that rosiglitazone significantly lowered blood sugar levels and hemoglobin A1c (HbA1c), levels of which are directly related to the risk of long-term complications. The FDA has placed the drug on a six-month priority review schedule; the compound also has priority revi... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855384 Mon, 10 Sep 2007 01:39:34 +0100 855384 http://www.medworm.com/index.php?rid=855383&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D81 Novartis's investigational compound tegaserod maleate (HTF-919, Zelmac[R]), a selective partial 5-HT4 receptor agonist, was the subject of several presentations at the recent Digestive Disease Week meeting. An aminoguanidine indole compound, tegaserod maleate is currently in phase III clinical trials for the treatment of irritable bowel syndrome (IBS). In a clinical study reported at DDW involving 24 patients with constipation-predominant IBS, tegaserod significantly accelerated orocecal transit time, proximal colonic emptying and scintigraphic colonic transit and appeared to facilitate colonic transit. These findings support those reported at the World Congress of Gastroenterology late last year, in which tegaserod treatment led to improvements in symptoms of abdominal discom... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855383 Mon, 10 Sep 2007 01:39:34 +0100 855383 http://www.medworm.com/index.php?rid=855382&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D82 In consideration of the wealth of information presented on new insulin analogues and insulin formulations under development during last month's meeting of the American Diabetes Association, three promising new insulins have been selected and are featured as the July 1999 Molecule of the Month. Novo Nordisk's insulin aspart (NovoRapid[TM]) is a long-acting insulin analogue that can be taken immediately before a meal. In a study in diabetic patients treated for up to 12 months, glycemic control was significantly better with insulin aspart than with human insulin. Furthermore, the incidence of potentially life-threatening hypoglycemic episodes occurring between midnight and 6:00 a.m. was significantly lower among subjects treated with the insulin analogue. Insulin aspart is under regulatory r... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855382 Mon, 10 Sep 2007 01:39:34 +0100 855382 http://www.medworm.com/index.php?rid=855381&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D83 The neuraminidase inhibitor zanamivir (Relenza®) has recently received regulatory approval in the United States and the European Union to be marketed for the treatment of influenza. In the United States, the approval comes after a three-month extension granted by the FDA to further review the New Drug Application (NDA) following the agency's Antiviral Drugs Advisory Committee meeting. In Europe, the approval was granted under the European Commission's mutual recognition procedure following approval of Relenza in February in Sweden. Relenza was launched in Australia, its first market, on May 1, 1999; it is also marketed in New Zealand. Zanamivir's mode of action is to prevent the spread of infection from one cell to another within the respiratory tract. The product is delivered via a s... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855381 Mon, 10 Sep 2007 01:39:34 +0100 855381 http://www.medworm.com/index.php?rid=855380&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D84 (Lotronex™) is a new 5-HT3 receptor antagonist specifically developed to address the multiple symptoms associated with diarrhea-predominant irritable bowel syndrome (IBS). Results from clinical studies have demonstrated significant and sustained pain relief and improvement in bowel function, especially in female patients. The product, developed by Glaxo Wellcome, was recently granted priority review status by the FDA as a potential drug addressing a major unmet medical need. (Source: Prous Science - Molecule of the Month) Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855380 Mon, 10 Sep 2007 01:39:34 +0100 855380 http://www.medworm.com/index.php?rid=855379&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D85 QuinupristinDalfopristin The streptogramins represent a novel class of antibiotics with a broad spectrum of activity against Gram-positive, Gram-negative and intracellular strains of bacteria, including many that are resistant to beta-lactams, macrolides, quinolones and glycopeptides. The most significant feature of the streptogramins is that they consist of two structurally unrelated molecular components which act in a synergistic fashion. The mechanism of activity of the streptogramins involves inhibition of protein synthesis. The two streptogramin components are, on the individual level, bacteriostatic; when they act in synergy, however, their effect is bactericidal and irreversible. The injectable streptogramin antibiotic Synercid(R) (quinupristin/dalfopristin), the first in its class... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855379 Mon, 10 Sep 2007 01:39:34 +0100 855379 http://www.medworm.com/index.php?rid=855378&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D86 Preliminary clinical results reported for first rhinovirus 3C protease inhibitor AG-7088 is a new rhinovirus 3C protease inhibitor undergoing early clinical development at Agouron Pharmaceuticals, Inc. (Warner-Lambert Co.) for the treatment of human rhinoviral infection. Company researchers presented preliminary clinical safety and pharmacokinetic data on the drug at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 26-29, 1999, in San Francisco. Intranasal AG-7088 was evaluated in double-blind, placebo-controlled, parallel trials in healthy volunteers following either single doses (4 or 8 mg; 12 subjects) or multiple doses (4 or 8 mg six times daily for seven days; 24 subjects) of 100 or 200 mcl sprayed into the nostrils. No clinically relev... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855378 Mon, 10 Sep 2007 01:39:34 +0100 855378 http://www.medworm.com/index.php?rid=855377&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D87 (formerly known as perprazole), the (S)-enantiomer of the marketed proton pump inhibitor omeprazole (Losec), has been developed by AstraZeneca as an improved second-generation successor to Losec with several advantages over the first-generation compound. Omeprazole has one significant known drawback: polymorphic metabolism. Approximately 3% of all Caucasian patients and some 15-20% of Oriental patients metabolize omeprazole more slowly than the general population. In slow metabolizers, plasma concentrations of the drug are higher than the average. Since the inhibition of gastric acid secretion is correlated to the plasma concentration AUC, these slow metabolizers experience a more pronounced effect from the drug. As such, the search was initiated for an improved version of omeprazole with... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855377 Mon, 10 Sep 2007 01:39:34 +0100 855377 http://www.medworm.com/index.php?rid=855376&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D20 (formerly TBC-11251) is a selective, orally, active, small-molecule endothelin ETA receptor antagonist under development at Texas Biotechnology. The compound has exhibited significant efficacy and good tolerance in patients with congestive heart failure and hypertension,and a phase II trial in pulmonary arterial hypertension was initiated in late 1999. A phase IIa study in congestive heart failure evaluating single i.v. bolus doses of sitaxsentan and placebo was terminated early due to the achievement of statistically significant results in the first 24 patients treated with drug. Based on these initial results, the protocol was subsequently amended to allow further evaluation of sitaxsentan at a higher dose. Again, significant improvement versus placebo was observed in central hemodynami... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855376 Mon, 10 Sep 2007 01:39:34 +0100 855376 http://www.medworm.com/index.php?rid=855375&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D21 Novartis Pharmaceuticals Corp.'s STI-571 (formerly CGP-57148), a tyrosine kinase inhibitor designed to block the Bcr-Abl protein responsible for chronic myelogenous leukemia (CML), has completed phase I trials with promising results and begun phase II trials in the United States and Europe. According to a clinical researcher who presented at the American Medical Association's 18th Annual Science Reports Conference in October 1999, STI-571 lowers white blood cell counts and actually alters abnormal cell structure to attack leukemia in patients with the disease. The results obtained to date in clinical studies with STI-571 were called "amazing" by the investigator. In the phase I trial conducted at UCLA, CML patients in the chronic stage (blast crisis) who failed to respond to conventional... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855375 Mon, 10 Sep 2007 01:39:34 +0100 855375 http://www.medworm.com/index.php?rid=855374&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D22 Given the epidemic proportions of hepatitis C around the world, the absence of an effective vaccine and the deficiencies in existing treatment options, new therapeutic agents for hepatitis C are being actively sought. Ribozymes are naturally occurring pieces of RNA that act as enzymes and perform numerous functions. Using the techniques of modern molecular biology, ribozymes can be designed as human therapeutics to recognize, bind and digest any disease-causing mRNA sequence. They can be chemically synthesized to selectively inhibit the production of disease-causing proteins through the specific cleavage of disease-causing mRNA. In addition, through chemical modifications, ribozymes can be made stable and active in human serum for several days. Ribozyme Pharmaceuticals has been working on ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855374 Mon, 10 Sep 2007 01:39:34 +0100 855374 http://www.medworm.com/index.php?rid=855373&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D23 Interferons (IFNs) have antiviral, antiproliferative and immunomodulatory effects and are used to treat a wide range of disorders. IFN-alpha and IFN-beta show predominantly antiviral effects that are nonspecific and are held to be due to blockade of the viral life cycle at several stages. Various interferons are currently marketed for the treatment of cancer, hepatitis B and C, and neurological disorders such as multiple sclerosis. Existing formulations, however, are hampered by their short half-lives and inconsistent pharmacokinetics; interferon alfa, for example, must be administered by subcutaneous injection several times weekly for a 12-month course in the treatment of hepatitis C. This fact led to the search for improved interferons that would maintain the proven therapeutic benefits ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855373 Mon, 10 Sep 2007 01:39:34 +0100 855373 http://www.medworm.com/index.php?rid=855372&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D37 Investigators from Novartis have described the potent antiglaucoma activity of SDZ-GLC-756, a benz[g]quinoline derivative with mixed dopamine D1 antagonist/D2 agonist activities. This dual mechanism of action is thought to be especially promising for the modulation of elevated intraocular pressure, given that D1 receptors mediate IOP increase while D2 receptors mediate IOP decrease. Concomitant blockade of D1 receptors and stimulation of D2 receptors could have at least additive IOP-lowering effects, thus presenting a unique and promising approach to the treatment of glaucoma. SDZ-GLC-756 demonstrated an excellent profile of activity in various experimental animal models as well as in glaucoma patients. Administered in an eye drop formulation, SDZ-GLC-756 (0.1-0.4%) decreased IOP in bo... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855372 Mon, 10 Sep 2007 01:39:34 +0100 855372 http://www.medworm.com/index.php?rid=855371&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D36 HCT-1026 (nitroflurbiprofen) is the lead compound in NicOx's family of NO-NSAIDs. These compounds, which incorporate nitric oxide linked to a nonsteroidal antiinflammatory drug, are designed to minimize the gastrointestinal and renal side effects of conventional NSAIDs by countering the prostacyclin deficiency and subsequent reduction in mucosal blood flow to target tissues associated with their administration. The NO-releasing compounds retain the well-documented therapeutic effects of NSAIDs, including analgesic, antiinflammatory and antithrombotic activities, and furthermore have potential application in additional indications currently not treatable with aspirin and related compounds. Two such indications are urinary incontinence and osteoporosis. The putative efficacy of NSAIDs, part... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855371 Mon, 10 Sep 2007 01:39:34 +0100 855371 http://www.medworm.com/index.php?rid=855370&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D35 The antibody immunoglobulin E (IgE) is at the top of the allergic cascade. Exposure to an allergen in a susceptible individual causes T-lymphocytes to become activated and send a signal to B-lymphocytes, initiating the production of IgE antibodies. For every allergen, specific IgE antibodies are produced within a few weeks after the first exposure. Some IgE antibodies bind to FcepsilonRI receptors on mast cells and eosinophils while others remain free, floating in the bloodstream. Mast cells in the skin and mucosal layers of the respiratory tract contain the inflammatory mediators that cause the symptoms of allergic rhinitis: histamine, leukotrienes and prostaglandins. These mediators are released every time that an allergen crosslinks mast cell-bound IgE. Reexposure to an allergen causes ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855370 Mon, 10 Sep 2007 01:39:34 +0100 855370 http://www.medworm.com/index.php?rid=855369&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D34 The new-generation, long-acting anticholinergic agent tiotropium bromide (Ba-679BR, Spiriva) is in phase III clinical development at Boehringer Ingelheim. This compound represents one of the most promising new drugs currently in the pipeline for chronic obstructive pulmonary disease (COPD), a common progressive lung disorder of increasing prevalence in industrialized countries. Bronchodilators are currently the mainstay for management of COPD. Within the bronchodilator class, anticholinergic agents appear to be more effective than short-acting beta2-adrenoceptor agonists. Anticholinergic agents block muscarinic receptors in airways, including M1 receptors on parasympathetic ganglia, M2 receptors on cholinergic nerve terminals and M3 receptors mediating the effects of acetylcholine on hum... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855369 Mon, 10 Sep 2007 01:39:34 +0100 855369 http://www.medworm.com/index.php?rid=855368&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D33 Three novel endothelin antagonists with promising efficacy in the treatment of congestive heart failure were discussed in depth at the recently concluded 18th Scientific Meeting of the International Society of Hypertension and the XXIInd Congress of the European Society of Cardiology: Knoll's darusentan, Actelion's tezosentan and Banyu's J-104132. Endothelin antagonists are considered to represent a promising new therapy for patients with a form of CHF characterized by high levels of endothelin and neurohormones, known to reflect poor prognosis. Darusentan (LU-135252), a selective endothelin ETA receptor antagonist, was shown in one study to have especially good activity in this particular patient group, producing significant hemodynamic and neurohumoral benefits at the end of a three-we... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855368 Mon, 10 Sep 2007 01:39:34 +0100 855368 http://www.medworm.com/index.php?rid=855367&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D32 In spite of the promise of 5alpha-reductase inhibitors for benign prostatic hyperplasia (BPH), only one compound to date has reached the market: Merck & Co.'s finasteride (Proscar). However, as a selective type 2 isozyme inhibitor, finasteride has proved only moderately effective in treating BPH and more potent compounds are clearly needed. Dutasteride (GI-198745) is a dual inhibitor of 5alpha-reductase type 1 and 2 isozymes which appears to be suitable for use alone or in combination with alpha1-adrenoceptor antagonists for the treatment of BPH and associated symptoms. Glaxo Wellcome is conducting phase III trials of the compound, with plans to file for regulatory approval in the U.S. and Europe this year. In a randomized, double-blind, parallel group 4-week study, dutasteride (40 m... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855367 Mon, 10 Sep 2007 01:39:34 +0100 855367 http://www.medworm.com/index.php?rid=855366&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D31 (BI-397) is a second-generation semisynthetic glycopeptide antibiotic belonging to the same class as vancomycin. The compound is under development at Versicor for the intravenous treatment of serious systemic infections caused by Gram-positive cocci, especially multidrug-resistant Staphylococcus aureus (MRSA) and S. epidermidis (MRSE). V-Glycopeptide has several advantages over vancomycin, most notably its increased potency against Gram-positive bacteria including MRSA and MRSE and an improved dosing regimen. Interim results from an ongoing phase I pharmacokinetic and safety trial were presented at the recent ICAAC meeting in Toronto. The antibiotic was well tolerated in healthy volunteers administered single or multiple i.v. infusions of V-glycopeptide at all dose levels tested. Serum ba... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855366 Mon, 10 Sep 2007 01:39:34 +0100 855366 http://www.medworm.com/index.php?rid=855365&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D30 Protein farnesylation, or the addition of 15-carbon isoprene units catalyzed by farnesyl protein transferase (FPT), permits the addition of a number of cellular proteins to cell membranes, where they mediate their effects. Farnesylated proteins -- including ras, rac, rho and other small G-proteins -- are involved in cell transformation and proliferation, and FPT inhibitors have emerged as one of the newer classes of antineoplastic agents. Mutated Ras oncogenes, in particular, play a causative role in malignant cell transformation and are frequently detected in human tumor cells. Inhibition of Ras oncoprotein farnesylation is considered an attractive target for development of antineoplastic agents. Five FPT inhibitors are currently in clinical testing, and preliminary evidence of clinical ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855365 Mon, 10 Sep 2007 01:39:34 +0100 855365 http://www.medworm.com/index.php?rid=855364&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D29 Fondaparin sodium (Org-31540/SR-90107A) is the first agent in a new class of antithrombotics --the selective factor Xa inhibitors. It acts on the two physiological pathways of the coagulation cascade and inhibits the generation of thrombin, thus inhibiting the formation and the growth of thrombi. The results of several phase II and phase III trials have been presented in the past few months. At the December meeting of the American Society of Hematology, fondaparin was reported to be the first antithrombotic to demonstrate a significant benefit over the comparator for the prevention of venous thromboembolism in three different types of orthopedic surgery: hip fracture, hip replacement and knee surgery. The results from four phase III clinical trials, all of which were multicenter, prospecti... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855364 Mon, 10 Sep 2007 01:39:34 +0100 855364 http://www.medworm.com/index.php?rid=855363&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D28 Rho kinase (p160ROCK) is an enzyme belonging to the rhoA/rho associated kinase pathway that regulates the state of phosphorylation of myosin phosphatase, leading to the control of smooth muscle contraction via a calcium- and nitric oxide (NO)-independent process. The rhoA/rho associated kinase pathway is functional in the cavernous circulation, and its blockade through Rho kinase inhibition strongly enhances the erectile response. This finding supports the utility of the selective Rho kinase inhibitor Y-27632 (Welfide) in the treatment of erectile dysfunction, a hypothesis that has been successfully put to the test in several animal models. Most recently, the intracavernosal injection of Y-27632 in rats was shown to significantly and dose-dependently increase the corpus cavernosum pressure... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855363 Mon, 10 Sep 2007 01:39:34 +0100 855363 http://www.medworm.com/index.php?rid=855362&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D27 Angiotensin converting enzyme (ACE) is produced in the endothelium of somatic tissues and is a pivotal member of the renin-angiotensin system. It mediates various local and systemic effects within the cardiovascular system by removing the carboxy terminal dipeptide from the decapeptide Ang I to generate Ang II. Blockade of ACE normalizes abnormally high systemic vascular tone, reversed cardiac myocyte hypertrophy and fibrosis. Captopril, the original member of the ACE-inhibitor class, was introduced in 1980 and has become a classic in the field of rational drug design. Nearly 20 ACE inhibitors are now available for clinical use. ACE inhibitors are recommended as first-line treatment for hypertensive patients with type 1 diabetes or with diabetic nephropathy due to their favorable effects o... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855362 Mon, 10 Sep 2007 01:39:34 +0100 855362 http://www.medworm.com/index.php?rid=855361&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D26 The selective cholesterol absorption inhibitor ezetimibe (Sch-58235), in late-stage clinical development at Schering-Plough, was the subject of presentations at two major congresses in March. Researchers presenting at the American Society of Clinical Pharmacology and Therapeutics (ASCPT) meeting in early March reported favorable results obtained in various clinical pharmacokinetic and interaction studies of ezetimibe in several patient populations. No pharmacokinetic or pharmacodynamic interactions were seen between ezetimibe and lovastatin, glipizide, warfarin or oral triphasic contraceptives in healthy volunteers. Another study confirmed that pharmacokinetics and tolerability in adolescents were comparable to those in adults, implying that no dose adjustments will be required in younger... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855361 Mon, 10 Sep 2007 01:39:34 +0100 855361 http://www.medworm.com/index.php?rid=855360&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D25 Creutzfeldt-Jakob disease (CJD), a transmissible spongiform encephalopathy that has traditionally been encountered at stable low levels (1 per one million population), has been on the increase in European countries in recent years, conceivably as a result of an epidemic a decade ago of bovine spongiform encephalopathy (BSE) in British cows that later entered the food chain. This invariably fatal neurodegenerative disease is believed to be caused by prions, an agent of disease transmission unlike better-known viruses, bacterial and other infectious microbes. When coincubated with the abnormal, disease-related form of the prion protein, cultured neuronal cells undergo a type of apoptotic cell death. Aoptosis inhibition has therefore been suggested as a promising therapeutic strategy. Various... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855360 Mon, 10 Sep 2007 01:39:34 +0100 855360 http://www.medworm.com/index.php?rid=855359&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D24 HMG-CoA reductase inhibitors, popularly known as statins, are among the most widely prescribed lipid-lowering drugs. Clinical trials have repeatedly demonstrated a reduction of approximately 30% in the relative risk of major coronary events, together with significant increases in survival, among patients receiving statin therapy. The Scandinavian Simvastatin Survival Study (4S) was the first to document reductions in all-cause mortality among patients with a history of angina pectoris or myocardial infarction treated with simvastatin. In this and other large prospective studies evaluating statins, plaque progression was reduced by an average of 30% with statin therapy, and clear plaque regression was observed in approximately 20% of patients administered drugs in this class. Al... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855359 Mon, 10 Sep 2007 01:39:34 +0100 855359 http://www.medworm.com/index.php?rid=855358&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D12 The rich structural and functional diversity of voltage-sensitive calcium channels (VSCC) provides excellent opportunities for the development of novel calcium (Ca2+) channel antagonists possessing unique pharmacodynamic properties. VSCCs are found in muscle tissues (skeletal, cardiac, smooth muscle) and the nervous system, where they are expressed in both neurons and neuroendocrine cells. By controlling the flow of calcium through plasma membranes, VSCCs regulate cytosolic calcium concentrations and thereby influence a host of cellular processes, including membrane excitability, signal transduction, intracellular metabolism and gene expression. Classical calcium channel blockers belonging to the dihydropyridine, phenylalkylamine and benzothiazepine families target L-type VSCCs expressed ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855358 Mon, 10 Sep 2007 01:39:34 +0100 855358 http://www.medworm.com/index.php?rid=855357&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D11 Endothelin antagonists are being actively investigated for several potential therapeutic applications - most in the area of cardiovascular disease - including arterial hypertension, pulmonary hypertension, congestive heart failure, asthma and erectile dysfunction. One selective endothelin ETA receptor antagonist, Abbott's atrasentan (ABT-627), is in late-stage clinical testing for a very different indication, prostate cancer. Promising results from efficacy and safety trials have been reported at recent scientific meetings. Atrasentan, a potent, orally active cytostatic agent, is currently entering phase III clinical evaluation in patients with hormone-refractory prostate cancer. Phase II data presented at ASCO's 2001 annual meeting demonstrated that the compound can inhibit the progressio... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855357 Mon, 10 Sep 2007 01:39:34 +0100 855357 http://www.medworm.com/index.php?rid=855356&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D10 Viral fusion is a complex process by which viruses attach to and penetrate host cells. If a virus cannot enter a host cell, it cannot replicate. Human immunodeficiency virus type I (HIV-1) is one such virus that relies on fusion to infect host cells. All existing AIDS drugs, in contrast, work at a later stage of infection: inside the cell, by targeting viral enzymes involved in the replication of the virus. Inhibition of infection at the earlier stage of viral fusion has been targeted as a potentially more effective method of preventing HIV and AIDS. Trimeris's T-20, the most advanced compound in development with this mechanism of action, inhibits fusion of HIV with host cells. T-20 is a synthetic peptide corresponding to a 36-amino-acid sequence within a C-terminal heptad repeat region of... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855356 Mon, 10 Sep 2007 01:39:34 +0100 855356 http://www.medworm.com/index.php?rid=855355&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D9 One of the most exciting findings in the AD research arena in recent years has been the development of a potential vaccine for Alzheimer's disease involving immunization with a modified form of Abeta peptide, the very peptide that triggers the deposition of amyloid plaque in patients with Alzheimer's disease. The immunization of transgenic mice bearing mutant forms of amyloid precursor protein (APP) was first reported in 1999 to provoke an immune response that increased the clearance of amyloid plaques from the brain. Immunization with AN-1792 (also known as AIP-001 or Betabloc), a synthetic form of the naturally occurring 42-amino acid Abeta protein (Abeta42), prevented the appearance of amyloid plaques and the neuropathology characteristic of Alzheimer's disease in young PDAPP mice. Immu... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855355 Mon, 10 Sep 2007 01:39:34 +0100 855355 http://www.medworm.com/index.php?rid=855354&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D8 Visceral leishmaniasis, also known as kala-azar, is a parasitic disease caused by infection of the spleen, liver, bone marrow and reticuloendothelial system. The infection results from the transmission of the leishmania parasite through sandfly bites, and is a significant health problem in Asia, South America and East Africa. If untreated, the disease is fatal. Existing treatment options include pentavalent antimonial agents, amphotericin B and liposomal amphotericin B. None of these consititute ideal treatment alternatives for the developing world, however, due to their route of administration (parenteral), high clinical failure rate (40% for pentavalent antimonial agents), side effects and cost (US $ 5,000 for liposomal amphotericin B). Thus the identification of an effective ant... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855354 Mon, 10 Sep 2007 01:39:34 +0100 855354 http://www.medworm.com/index.php?rid=855353&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D7 Lilly's drotrecogin alfa (activated), a breakthrough drug for reducing mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death, was approved by the U.S. FDA in late November 2001. The company said it planned to introduce the drug within a few days of approval. The approval was based on the results of a landmark international phase III clinical trial known as PROWESS, which were published in March in the New England Journal of Medicine. To be marketed under the trade name Xigris, drotrecogin alfa is a recombinant form of human activated protein C. Sepsis is a syndrome characterized by an extreme systemic response to infection that can quickly lead to multiple organ failure and death. Sepsis is the cause of death in more... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855353 Mon, 10 Sep 2007 01:39:34 +0100 855353 http://www.medworm.com/index.php?rid=855352&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D6 (formerly SDZ-ASM-981), an ascomycin macrolactam derivative and selective inhibitor of inflammatory cytokines, has been successfully developed by Novartis as a novel nonsteroidal topical treatment for atopic dermatitis. Clinical trials involving more than 1,700 adult and pediatric patients with atopic dermatitis have confirmed that pimecrolimus, which acts by inhibition the production and release of inflammatory cytokines (IL-2 and TNF-alpha) from T cells, is able to reduce the itching and redness associated with eczema within eight days of beginning treatment. The good tolerability of topical pimecrolimus has been demonstrated in infants as young as three months, and efficacy has been demonstrated in a wide range of patients. Results from two multicenter, randomized, double-blind, vehic... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855352 Mon, 10 Sep 2007 01:39:34 +0100 855352 http://www.medworm.com/index.php?rid=855351&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D5 Although oxygen is central to life, the body's utilization of this gas also results in the production of the undesirable metabolic by-product superoxide, a toxic free radical that can damage cellular components. In normal circumstances, the natural superoxide dismutase (SOD) enzymes catalytically remove superoxide by converting it into oxygen and hydrogen peroxide, which is quickly decomposed by another abundant enzyme, catalase. In its defense against pathogens, our immune system generates superoxide, which is converted first to hydrogen peroxide and then to hypochlorite, the active ingredient in chlorine bleach. Hypochlorite is the body's chemical antiseptic. Superoxide dismutase is, therefore, an essential component in converting superoxide to the antibacterial agent, hypochlorite. In d... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855351 Mon, 10 Sep 2007 01:39:34 +0100 855351 http://www.medworm.com/index.php?rid=855350&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D4 The life cycle of the HIV virus is exceptionally well characterized. It begins when HIV enters its host cell through membrane fusion. The viral gp120/gp41 membrane glycoprotein complex first binds to the cellular transmembrane protein CD4, present on T helper cells and macrophages. Binding induces a conformational change in gp120/gp41, leading to binding of yet another cellular transmembrane glycoprotein ("coreceptor"), typically a molecule belonging to the class of chemokine receptors. For primary virus strains transmitted from one patient to the next, this coreceptor is frequently CCR5 present on macrophages; evolution of the virus in the body of an infected patient gives rise to strains that recognize predominantly the coreceptor CXCR4, present on T cells. Other coreceptors have been de... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855350 Mon, 10 Sep 2007 01:39:34 +0100 855350 http://www.medworm.com/index.php?rid=855349&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D3 Photodynamic therapy (PDT) is an emerging treatment modality based on the interaction of light, a photosensitizing drug and oxygen. PDT has promising applications in areas of cardiology, oncology, dermatology, ophthalmology and gynecology. To date, the major obstacle to the widespread use of PDT has been the lack of a suitable photosensitizer. Limitations of current photosensitizers include toxicity, inability to treat deeply situated cancers, cutaneous photosensitivity and water insolubility. Pharmacyclics' investigational photodynamic therapy agent, motexafin lutetium, is a novel photosensitizing agent designed to overcome these limitations. Motexafin lutetium has the potential to combine the features of selective localization, ability to be activated by deeply penetrating far-red light... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855349 Mon, 10 Sep 2007 01:39:34 +0100 855349 http://www.medworm.com/index.php?rid=855348&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D2 AtheroGenics' AGI-1067 is the first in a promising new class of orally available compounds known as composite vascular protectants, or v-protectants. Composite v-protectants are small-molecule phenolic antioxidants with a dual mechanism of action that involves protecting the arterial lining and lowering LDL cholesterol levels. AGI-1067 functions as a v-protectant by blocking the production of a selective set of inflammatory genes, including VCAM-1 and MCP-1, which have been implicated in the initiation and progression of atherosclerosis. AGI-1067 is currently in phase II testing for the treatment of atherosclerosis and postangioplasty restenosis. The CART-1 (Canadian Antioxidant Restenosis Trial) phase II clinical studies in 305 postangioplasty patients showed that compound (70, 140 or 280... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855348 Mon, 10 Sep 2007 01:39:34 +0100 855348 http://www.medworm.com/index.php?rid=855347&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D1 AstraZeneca's novel anticancer agent gefitinib (ZD-1839, IressaTM) was the subject of several presentations made in late May 2002 at the American Society of Clinical Oncology's 38th Annual Meeting in Orlando, Florida. This promising new chemotherapeutic drug is reported to possess outstanding therapeutic efficacy and excellent tolerability in patients with non-small cell lung cancer (NSCLC) as well as advanced head and neck cancer. Regulatory filings have been made in the U.S. and Japan for the NSCLC indication, and the company plans to follow suit in the European Union during the second quarter of 2002. Gefitinib is also in phase III clinical trials for the treatment of breast, colorectal, prostate and gastric cancers. Gefitinib acts by targeting and blocking the epidermal growth factor ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855347 Mon, 10 Sep 2007 01:39:34 +0100 855347 http://www.medworm.com/index.php?rid=855346&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D38 Sivelestat sodium hydrate (Ono-5046, Elaspol[TM]) is an injectable selective inhibitor of human neutrophil elastase that was jointly developed by Lilly and Ono for the treatment of acute lung injury associated with systemic inflammatory response syndrome (SIRS). Treatment with the agent has been shown to improve respiratory function and facilitate early removal of patients from mechanical ventilation which could reduce the development of ventilator-associated pneumonia and patient stay in intensive care. Sivelestat sodium hydrate has also displayed activity in a rat model of lower limb ischemia/reperfusion injury when the agent was administered following ischemia and before reperfusion resulting in significant and dose-dependent reductions in elevated creatine phosphokinase (CPK) levels at... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855346 Mon, 10 Sep 2007 01:39:34 +0100 855346 http://www.medworm.com/index.php?rid=855345&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D39 Human trials will soon begin with the unique topical DNA vaccine DermaVir(TM) developed by Genetic Immunity and Georgetown University's Research Institute for Genetic and Human Therapy ("RIGHT") to prevent HIV-positive individuals from developing AIDS. DermaVir(TM), a plasmid DNA encoding for viral proteins, is applied to the skin, where it is taken up by Langerhans cells which then migrate to the lymph nodes and mature to SIV/HIV antigen-expressing dendritic cells that elicit potent HIV-specific immunity and eliminate HIV-infected cells. The vaccine is hypothesized to mimic, in chronically infected patients, the T-cell-mediated immunity induced in early infection using highly active antiretroviral therapy together with structured treatment interruptions (STI-HAART). Results from two stu... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855345 Mon, 10 Sep 2007 01:39:34 +0100 855345 http://www.medworm.com/index.php?rid=855344&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D40 Novartis' novel selective cyclooxygenase type 2 (COX-2) inhibitor lumiracoxib (COX-189, Prexige[TM]) is currently under phase III clinical investigation for the treatment of arthritis and pain and was the subject of several presentations made in late June 2002 at the EULAR- Annual European Congress of Rheumatology in Stockholm, Sweden. Studies performed in vitro revealed that the COX-2 selectivity of lumiracoxib was 100- and 1,400-fold higher than that of diclofenac and naproxen, respectively. Phase II efficacy, safety and tolerability data presented at the meeting support the potential clinical use of the agent. Lumiracoxib at a daily dose of 400 mg was as effective as diclofenac (75 mg b.i.d.) in the treatment of patients with osteoarthritis. The gastrointestinal safety profile of the ag... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855344 Mon, 10 Sep 2007 01:39:34 +0100 855344 http://www.medworm.com/index.php?rid=855343&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D41 In September 2002, Gilead's adefovir dipivoxil (Hepsera™) became the first nucleotide analogue to be approved by the FDA for the treatment of chronic hepatitis B (HBV). The specific approved indication for the drug is the oral treatment of chronic HBV in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Adefovir blocks the replication of the hepatitis B virus through inhibition of viral enzymes. In clinical studies, it has provided significant improvement in liver histology and fibrosis, reductions in serum HBV DNA levels, increased rates of seroconversion and normalization of ALT levels compared to placebo in both treatment-naive patients and those previously treated... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855343 Mon, 10 Sep 2007 01:39:34 +0100 855343 http://www.medworm.com/index.php?rid=855342&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D42 Fungi and humans are both eukaryotes, therefore new antifungal compounds must focus on fungus-specific targets in order to minimize potential toxicity to the human host. Biosynthesis of the fungal cell wall offers many potential pathogen-specific therapeutic targets. Foremost among compounds acting on these cell wall targets in Candida sp., Aspergillus sp. and Pneumocystis carinii are the 1,3-ß-D-glucan synthesis inhibitors. A new class of compounds called the echinocandins inhibits this key enzyme system. The echinocandins represent the first new class of antifungal drugs to reach the market in more than 15 years. The echinocandins are a class of synthetically modified lipopeptides that were originally derived from the fermentation broths of various fungi. They have several advantag... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855342 Mon, 10 Sep 2007 01:39:34 +0100 855342 http://www.medworm.com/index.php?rid=855341&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D88 Otsuka and Bristol-Myers Squibb have received FDA approval to market aripiprazole (Abilify™) as a new treatment for schizophrenia. Aripiprazole represents the first of a new generation of atypical antipsychotics, the dopamine/serotonin system stabilizers. It has shown potent partial agonism of dopamine D2 receptors, associated with partial agonism of 5-HT1A receptors and antagonism of 5-HT2 receptors. Stabilizing the dopamine and 5-HT systems is thought to be vital for the management of schizophrenia symptoms. Clinical studies in more than 3,400 patients with acute relapse of schizophrenia demonstrated that treatment with aripiprazole for up to 52 weeks provided significant improvement in both positive and negative symptoms. Moreover, treatment with aripiprazole was associated with ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855341 Mon, 10 Sep 2007 01:39:34 +0100 855341 http://www.medworm.com/index.php?rid=855340&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D89 The hormonal regulation of insulin secretion in response to glucose involves pancreatic and gastrointestinal hormones. The insulin response to glucose is much more pronounced when glucose is administered orally as compared to intravenously, due to the intervention of a class of gut-derived insulin-releasing hormonal factors called incretins. The major incretins are gastric inhibitory polypeptide (GIP) and the truncated form of glucagon-like peptide-1 (GLP-1). When blood glucose levels are elevated, incretins act on the pancreas to potentiate glucose-induced insulin secretion. GIP and GLP-1 have thus been proposed as potential agents for the treatment of diabetes. These hormones, however, are rapidly hydrolyzed by the circulating hormone dipeptidyl peptidase IV (DPP IV) and are only active ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855340 Mon, 10 Sep 2007 01:39:34 +0100 855340 http://www.medworm.com/index.php?rid=855339&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D13 There is increasing evidence that malfunctioning of glutamatergic neurotransmission, and particularly of N-methyl-D-aspartate (NMDA) receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia. Based on this evidence, researchers at Merz have developed the voltage-dependent, moderate-affinity, uncompetitive NMDA antagonist memantine hydrochloride as a new treatment for Alzheimer's disease. Approved in the E.U. and launched by Merz last year for the first time in Germany, memantine hydrochloride (Axura(R)) is the first AD therapeutic to act via this mechanism of action; all other drugs marketed to date for this indication (e.g., tacrine, donepezil) act as acetylcholinesterase inhibitors. Memantine has been marketed for 20 years, although only ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855339 Mon, 10 Sep 2007 01:39:34 +0100 855339 http://www.medworm.com/index.php?rid=855338&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D14 Strontium ranelate, a promising new osteoporosis therapeutic in late-stage development at Servier, is the first agent to stimulate the formation of new bone as well as prevent loss of existing bone, and therefore represents a major advance in the treatment of this highly prevalent disease. Unlike existing therapies, for osteoporosis all of which are designed to limit the loss of existing bone (antiresorptive agents), strontium ranelate has anabolic effects and thus is doubly effective in increasing bone strength and density. The results of two major randomized, double-blind, placebo-controlled long-term studies support the efficacy of strontium ranelate in osteoporosis. STRATOS (STRontium Administration for Treatment of Osteoporosis) and PREVOS (PREVention of Osteoporosis Study) were two... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855338 Mon, 10 Sep 2007 01:39:34 +0100 855338 http://www.medworm.com/index.php?rid=855337&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D15 The selective immunosuppressant FTY-720, discovered by Mitsubishi Pharma and licensed to Novartis, is in phase II testing in the U.S. and Europe for the prevention of acute rejection and graft loss in kidney transplant patients. FTY-720 was synthesized using a component of the Isaria sinclairii fungus and has a novel mechanism of action, via which it protects transplanted organs against T cells without affecting the host's ability to respond to antigens. Specifically, it inhibits apoptosis and inhibits lymphocyte recirculation by activating sphingosine-1-phosphate (S1P) receptors. Acute rejection rates with FTY-720 in clinical trials to date have been very low as compared to low-dose ciclosporin (Neoral®). Synergistic efficacy has been observed in combination with Neoral or with everol... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855337 Mon, 10 Sep 2007 01:39:34 +0100 855337 http://www.medworm.com/index.php?rid=855336&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D16 Malaria is a serious but preventable disease caused by the bite of an infected mosquito. There are four kinds of malaria that can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Malaria occurs in over 100 countries and territories. More than 40% of the people in the world are at risk. Large areas of Central and South America, Africa, the Indian subcontinent, Southeast Asia, the Middle East and Oceania are considered malaria-risk areas. The World Health Organization estimates that yearly 300-500 million cases of malaria occur and more than 1 million people die of malaria. Antimalarial drugs, when used as monotherapies, are rapidly losing their effectiveness. In some places, malaria is resistant to all affordable first-line therapies. Drug-resistant strains of... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855336 Mon, 10 Sep 2007 01:39:34 +0100 855336 http://www.medworm.com/index.php?rid=855335&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D17 (Velcade™, PS-341, LDP-341, MLN-341) is a proteasome inhibitor developed by Millennium that induces apoptosis in cancer cells and inhibits both binding to stromal cells and the production of growth and survival factors by multiple myeloma cells in the bone marrow. The proteasome is an enzyme complex within the cell responsible for breaking down proteins that have been marked for removal by the attachment of a tag called ubiquitin. The ubiquitin-proteasome pathway plays an essential role in regulating the concentration of specific proteins inside the cell, thereby maintaining homeostasis, the natural tendency of the cell to remain stable. Inhibition of the proteasome prevents this targeted proteolysis which can affect multiple signaling cascades within the cell. This disruption of no... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855335 Mon, 10 Sep 2007 01:39:34 +0100 855335 http://www.medworm.com/index.php?rid=855334&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D18 is the flagship member of a new class of potential antianginal drugs called partial fatty acid oxidation (pFOX) inhibitors. pFOX inhibitors have the potential to become the first new class of antianginal drugs to reach the U.S. market in more than two decades. Angina attacks occur when the heart does not receive all the oxygen it requires to function properly. Partial fatty acid oxidation inhibitors alter the metabolism of the heart to make it use oxygen more efficiently during times of stress. Under ischemic conditions, heart muscle cells use more fatty acid and less glucose, but the former is less oxygen-efficient. pFOX inhibitors reduce fatty acid oxidation and maintain glucose oxidation. Since glucose metabolism produces more energy per unit of oxygen than fatty acid metabolism, this... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855334 Mon, 10 Sep 2007 01:39:34 +0100 855334 http://www.medworm.com/index.php?rid=855333&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D19 (AMG-073) is a calcimimetic agent that has proven effective in the treatment of secondary hyperparathyroidism, a common complication of chronic kidney disease. The drug increases the sensitivity of the calcium receptor in the parathyroid gland to extracellular calcium and thereby reduces the levels of parathyroid hormone (PTH). It is currently undergoing phase III trials at Amgen, which is developing the drug under license from NPS Pharmaceuticals. Amgen plans to file an NDA for cinacalcet hydrochloride during the second half of 2003. Several presentations at the World Congress of Nephrology (June 2003, Berlin) supported the excellent therapeutic activity and long-term efficacy of cinacalcet in patients with secondary hyperparathyroidism. A randomized, double-blind clinical trial that en... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855333 Mon, 10 Sep 2007 01:39:34 +0100 855333 http://www.medworm.com/index.php?rid=855332&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D64 Inspire Pharmaceuticals' diquafosol tetrasodium (INS-365) is a P2Y2 receptor agonist that activates receptors on the ocular surface and inner lining of the eyelid to stimulate the release of water, salt, mucin and lipids -- the key components of natural tears. An NDA for diquafosol tetrasodium ophthalmic solution as a treatment for dry eye was submitted in June 2003. Inspire expects to receive a decision from the agency by the end of 2003, and to launch the product next year. In June 2001, Inspire entered into a partnership with Allergan for the development and commercialization of diquafosol tetrasodium outside of Asia. Santen is developing diquafosol in Japan and nine other Asian countries. The company has reported encouraging results from study 03-108, a phase IIIb study of the P2Y2 ag... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855332 Mon, 10 Sep 2007 01:39:34 +0100 855332 http://www.medworm.com/index.php?rid=855331&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D90 The hormonal regulation of insulin secretion in response to glucose involves pancreatic and gastrointestinal hormones. The insulin response to glucose is much more pronounced when glucose is administered orally as compared to intravenously, due to the intervention of a class of gut-derived insulin-releasing hormonal factors called incretins. When blood glucose levels are elevated, incretins act on the pancreas to potentiate glucose-induced insulin secretion. The major incretins are gastric inhibitory polypeptide (GIP) and the truncated form of glucagon-like peptide-1 (GLP-1). An ideal treatment for type 2 diabetes would be able to perform three major therapeutic effects: 1) lower blood glucose levels without concomitant hypoglycemia; 2) decrease blood glucagon levels; and 3) slow down gast... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855331 Mon, 10 Sep 2007 01:39:34 +0100 855331 http://www.medworm.com/index.php?rid=855330&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D91 Eli Lilly & Co.’s investigational compound ruboxistaurin mesilate hydrate (LY-333531), a protein kinase C beta (PKC beta) inhibitor, is in clinical testing for the treatment of microvascular complications (diabetic retinopathy, peripheral neuropathy and nephropathy) in patients with diabetes mellitus. Preclinical data show that ruboxistaurin is a specific inhibitor of PKC beta, an enzyme that has been implicated in the underlying process of microvascular damage. Because type 2 diabetes is often not diagnosed until years after onset, many patients already have diabetic microvascular complications at diagnosis; three of four patients with diabetes develop at least one complication within 15 years of diagnosis. Clinical trial results presented at major diabetes congresses last summer ha... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855330 Mon, 10 Sep 2007 01:39:34 +0100 855330 http://www.medworm.com/index.php?rid=855329&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D92 (TMX-67) is a selective inhibitor of xanthine oxidase/xanthine dehydrogenase under development for the treatment of gout and hyperuricemia. Febuxostat is expected to be safer and more effective than allopurinol, the only xanthine oxidase inhibitor presently on the market, at lower doses. The drug, discovered by Teijin, is currently in phase III trials in Japan (Teijin) and the U.S. (TAP Pharmaceutical) and it was recently licensed to Ipsen for Europe. Febuxostat was the focus of several presentations at the recent American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) meeting. A multicenter, double-blind, randomized, placebo-controlled clinical trial evaluated the efficacy and tolerability of febuxostat in 128 Japanese patients with gout or hyperuric... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855329 Mon, 10 Sep 2007 01:39:34 +0100 855329 http://www.medworm.com/index.php?rid=855328&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D93 Thrombin, a trypsin-like serine protease, is the final enzyme in the coagulation cascade formed from prothrombin via the serine protease factor Xa. Thrombin plays several key roles in the coagulation cascade. It induces platelet aggregation and, through positive feedback and activation of factors Va, VIIIa and XI, it enhances its own production. Small-molecule thrombin inhibitors are classified into two subtypes: tripeptide and peptide mimetics of the fibrinogen cleavage site and nonpeptide inhibitors. One of the more interesting compounds in this class is AstraZeneca's ximelagatran (H-376/95), a small-molecule double prodrug of the non-covalent peptide thrombin inhibitor melagatran, which exhibits poor bioavailability and absorption upon oral dosing. Following oral administration, the pro... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855328 Mon, 10 Sep 2007 01:39:34 +0100 855328 http://www.medworm.com/index.php?rid=855327&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D94 The rapamycin analogue everolimus (Certican[R]; formerly SDZ-RAD) is a novel proliferation signal (mTOR) inhibitor with immunosuppressive properties that targets the primary causes of allograft dysfunction. The drug has been repeated shown to reduce the incidence of acute rejection, reduce calcineurin inhibitor-induced nephrotoxicity, decrease the incidence of cytomegalovirus (CMV) infections and inhibit vascular remodeling. An extensive clinical trial program has demonstrated that everolimus is able to target primary causes of chronic rejection, including progressive vasculopathy, which eventually develops in approximately 50% of all transplant recipients in the first several years after surgery. Twenty-four month data from a major international trial involving more than 600 heart tra... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855327 Mon, 10 Sep 2007 01:39:34 +0100 855327 http://www.medworm.com/index.php?rid=855326&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D95 Inhaled corticosteroids are the gold standard in asthma maintenance therapy, and systemic corticosteroids are used to treat severe exacerbations of asthma in the hospital setting. Corticosteroids have been marketed for this indication since the 1950s. In the asthmatic patient, corticosteroids decrease bronchial hyperreactivity and improve lung function, symptomatology and quality of life. Nonetheless, corticosteroids are not curative and their therapeutic benefits disappear when they are discontinued. Inhaled corticosteroids are considered to be safe and are generally well tolerated, although they can produce side effects. Even if a corticosteroid is properly inhaled, approximately 70-80% of the dose is swallowed. This portion can be absorbed by the gastrointestinal tract and can caus... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855326 Mon, 10 Sep 2007 01:39:34 +0100 855326 http://www.medworm.com/index.php?rid=855325&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D96 The betulinic acid derivative PA-457 is the first in the new class of antiretroviral agents called maturation inhibitors. It has a mechanism of action different from those of approved HIV drugs and potent activity against both wild-type HIV and strains resistant to current therapies, including inhibitors of reverse transcriptase and viral protease. PA-457 inhibits viral replication by disrupting a late stage in Gag processing, a series of events required for the process of structural rearrangement that is known as virus maturation. During maturation, the immature virus particle makes the transition to a mature, infectious virion. PA-457 prevents this event by interrupting the conversion of the capsid precursor (p25) to a mature capsid protein (p24), resulting in the formation of defective,... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855325 Mon, 10 Sep 2007 01:39:34 +0100 855325 http://www.medworm.com/index.php?rid=855324&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D97 High-density lipoprotein (HDL) is one of the major lipid-transporting elements in the blood. It is known as the "good" cholesterol because it transports excess lipids from peripheral cells in the arterial walls to the liver, where they are subsequently eliminated in bile. Enhancement of this process --known as reverse cholesterol transport (RCT) or reverse lipid transport (RLT)—by boosting levels of HDL cholesterol has in recent years emerged as an attractive strategy for the control of atherosclerosis. Cholesteryl ester transfer protein (CETP) plays a pivotal role in the metabolism of HDL cholesterol, and has been identified as a potential factor influencing whether or not patients respond favorably to lipid-lowering therapy with statins and other drugs. CETP regulates the exchange of ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855324 Mon, 10 Sep 2007 01:39:34 +0100 855324 http://www.medworm.com/index.php?rid=855323&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D98 Alteon’s alagebrium chloride (ALT-711) is the first in a new class of compounds that have been shown in vitro and in vivo to reverse advanced glycation end-product (AGE) crosslinking, thereby restoring more normal function to tissues, vessels and organs that have lost flexibility. Alagebrium's mechanism of action is believed to be new and novel, and unrelated to that of any pharmaceutical agent. Alagebrium does not disrupt the natural enzymatic glycosylation sites or peptide bonds that are responsible for maintaining the normal integrity of the collagen chain. In preclinical studies, alagebrium consistently demonstrates the ability to reverse the upregulation of genes for proteins and growth factors known to be associated with the pathological hypertrophy of tissues. Alagebrium has demon... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855323 Mon, 10 Sep 2007 01:39:34 +0100 855323 http://www.medworm.com/index.php?rid=855322&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D99 Cannabinoid receptors are members of the G-protein-coupled receptor superfamily. The cannabinoid-1 (CB1) receptor subtype is widely distributed in central and peripheral organs including the brain, adipose tissues, gastrointestinal, pulmonary, reproductive and cardiovascular systems. The CB1 receptor is involved in the regulation of energy balance and body weight but also in reinforcing reward. Rimonabant hydrochloride (Acomplia™; Sanofi-Synthélabo), the first of a new class of selective CB1 receptor antagonists, is envisioned as an eventual cornerstone in the management of patients with cardiovascular risk factors. Rimonabant was evaluated in two programs, the RIO program and the STRATUS program. The RIO program has enrolled a total of over 6,600 patients in four phase III t... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855322 Mon, 10 Sep 2007 01:39:34 +0100 855322 http://www.medworm.com/index.php?rid=855321&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D100 Obesity is one of the most common metabolic disorders in the world. According to the Centers for Disease Control and Prevention, nearly two-thirds of the adult population of the United States, the country with the highest prevalence of obesity worldwide, is overweight and more than half of these are frankly obese. The World Bank estimates that obesity alone accounts for more than 12% of the U.S. national health care budget. The National Institutes of Health estimated that direct costs for the treatment of obesity in 1998 had reached $102.2 billion dollars. As these statistics illustrate, obesity is a rapidly growing, costly disease, for which there is currently no effective treatment. Existing medications for the treatment of obesity have significant side effects that limit their u... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855321 Mon, 10 Sep 2007 01:39:34 +0100 855321 http://www.medworm.com/index.php?rid=855320&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D101 Millions of people worldwide suffer from various forms of vascular disease. In the E.U. alone more than 2 million people are hospitalized and an estimated 4 million patients per year undergo invasive, catheter-based X-ray angiography (XRA), the most widely used method of vascular imaging. In the U.S., an estimated 62 million people have some form of cardiovascular disease, and approximately 4.8 million angiograms were performed in the US in 2002 in the cerebral, carotid, renal, and other peripheral arteries. It is currently estimated that only 25% of the 10 million Americans affected by peripheral vascular disease have been diagnosed, however. Given the risks that are associated with catheter X-ray angiography, many patients are contraindicated for either the X-ray contrast agent or th... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855320 Mon, 10 Sep 2007 01:39:34 +0100 855320 http://www.medworm.com/index.php?rid=855319&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D103 Duloxetine hydrochloride, a balanced and potent dual inhibitor of serotonin and norepinephrine reuptake, was developed simultaneously by Lilly for two apparently unrelated indications: depression and stress urinary incontinence (SUI). A huge body of clinical evidence supports its efficacy for both indications: duloxetine has been studied in more than 6,000 adults with major depression worldwide, showing improvements in both the emotional and physical symptoms of depression. Another 10 studies in more than 2,000 women with SUI across 5 continents demonstrated that duloxetine effectively reduces the frequency of incontinence episodes by up to 53% and is generally well tolerated. In patients with incontinence, duloxetine increases neurotransmitter concentrations; this is believed to increase ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855319 Mon, 10 Sep 2007 01:39:34 +0100 855319 http://www.medworm.com/index.php?rid=855318&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D104 Parkinson’s disease (PD) is an age-related, progressive, neurodegenerative disease affects as many as 1 million people in the U.S. alone and up to 4 million worldwide. It is caused by the death of cells that produce dopamine, a neurotransmitter necessary for normal motor function. Parkinson's patients suffer from tremors, rigidity, slow or uncontrolled muscle movement, speech disorders, and gait and postural disturbances. Administration of drugs designed to enhance or increase endogenous dopamine levels represents the most widely used and firmly established method of treating Parkinson's disease. Various dopamine-increasing strategies have been identified, although the most widely used continues to be administration of the dopamine precursor levodopa. Long-term use of levodopa can be ass... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855318 Mon, 10 Sep 2007 01:39:34 +0100 855318 http://www.medworm.com/index.php?rid=855317&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D105 With the emergence of organisms such as quinolone-resistant pneumococci and methicillin-, quinolone- and glycoprotein-intermediate and -resistant staphylococci, the need for novel agents to treat community-acquired respiratory and skin and soft tissue infections is a priority. A novel class of antibacterial agents to emerge from research efforts are the peptide deformylase inhibitors. Prokaryotic translation produces proteins that all begin with N-formyl methionine, a residue that is commonly removed in a multiple step process that begins with deformylation mediated by the enzyme, peptide deformylase (EC 3.5.1.88). Later steps in this process cannot proceed in the presence of the formyl group and often the resulting protein is not biologically active with the N-terminal Met in place. Inact... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855317 Mon, 10 Sep 2007 01:39:34 +0100 855317 http://www.medworm.com/index.php?rid=855316&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D131 Epilepsy constitutes a group of chronic disorders characterized by spontaneous disturbances of the normal electrical activity of the brain. About 5% of the world population will have a seizure during the course of their lifetime and of these 10-20% will develop repeated seizures. Only reoccurring seizures are called epilepsy. About 1% of the world population suffers from epilepsy, making it second most prevalent neurological disorder. Most antiepileptic drugs increase the threshold of electrical energy in the epileptic focus required for a seizure to occur. Every human being has a brain seizure threshold, which makes people more or less resistant to seizures. Epileptic patients have an abnormally low seizure threshold that can be normalized with the help of treatment. Strateg... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855316 Mon, 10 Sep 2007 01:39:34 +0100 855316 http://www.medworm.com/index.php?rid=855315&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D132 Alzheimer's disease is a degenerative neurological condition affecting nearly half of those over 85, with an estimated 4 million cases in the United States alone. Current approved treatments, such as cholinesterase inhibitors, temporarily relieve symptoms without meaningfully impacting progression of the underlying disease. Alzheimer's disease is marked by progressive cognitive decline and by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major structural component of these plaques is amyloid beta peptide, specifically amyloid beta-42 (Abeta42). Many researchers now believe that Abeta42 plays an essential role in initiating the neurodegeneration leading to the onset of Alzheimer's disease. Current research is focused on compounds that decrease levels of A... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855315 Mon, 10 Sep 2007 01:39:34 +0100 855315 http://www.medworm.com/index.php?rid=855314&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D133 The Ras proteins have become a target for the development of anticancer drugs due to the fact that oncogenic mutations have been identified in approximately 30% of all known human malignancies. Due to the crucial role farnesylation plays in Ras maturation, inhibitors of farnesyl protein transferase have emerged as a novel class of antineoplastic agents. Inhibitors of this enzyme ultimately interfere with ras-dependent cell transformation and therefore selectively inhibit the growth of ras-transformed cells. The investigational response has been the development of several farnesyl protein transferase inhibitors. Several of these agents are in the advanced stage of preclinical testing or in clinical trials, the most advanced being Johnson & Johnson’s tipifarnib. Tipifarnib, adminis... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855314 Mon, 10 Sep 2007 01:39:34 +0100 855314 http://www.medworm.com/index.php?rid=855313&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D134 Insulin sensitizers, or enhancers of insulin action, improve insulin resistance in patients with type 2 diabetes by increasing the sensitivity of cells to insulin, enabling the hormone to transport glucose from the blood into cells. Within the insulin sensitizer class, PPAR agonists have emerged as an especially promising class of antidiabetic agents, The peroxisome proliferator-activated receptor (PPAR) family of transcription factors plays a key role in regulating dietary fat storage and catabolism. Since they were first cloned just a decade ago, the PPARs have become established as an important target for the treatment of type 2 diabetes, obesity, cardiovascular disease, metabolic syndrome and other human health disorders associated with high intake of dietary fat. Three receptor subtyp... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855313 Mon, 10 Sep 2007 01:39:34 +0100 855313 http://www.medworm.com/index.php?rid=855312&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D135 Postoperative ileus (POI) is defined as transient impairment of gastrointestinal motility and function characterized by abdominal distension and pain, nausea and vomiting, reduced desire to eat, and an inability to pass flatus (gas) or stool. POI may be brought on by manipulation of the bowel during surgery; and opioid use during and after surgery may prolong recovery from POI. Nearly all patients undergoing open abdominal surgery are at risk for the condition, which is associated with prolongation of hospital stay and increased healthcare costs. Currently there are no marketed treatments for postoperative ileus, and the condition has been identified by healthcare professionals as an important unmet medical need. Alvimopan hydrate (Adolor/GlaxoSmithKline) is an investigational peripherally... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855312 Mon, 10 Sep 2007 01:39:34 +0100 855312 http://www.medworm.com/index.php?rid=855311&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D136 The finding that the ErbB (HER) family of tyrosine receptor kinases is involved in the mediation of cell growth, survival and treatment resistance of different epithelial tumors led to the development of therapies that specifically target these proteins. ErbB2 (HER2/neu) is a member of this family that has been found to be especially relevant in some patients with breast cancer and other carcinomas. Lapatinib (GW-572016; GlaxoSmithKline) is a small molecule that inhibits the activity of both ErbB1 and ErbB2, and has shown clinical activity in breast cancer. As a reversible and dual-acting inhibitor, investigators hope that the drug will be able to overcome problems of resistance encountered with single inhibitors. Encouraging data regarding the antitumor activity of lapatinib were presente... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855311 Mon, 10 Sep 2007 01:39:34 +0100 855311 http://www.medworm.com/index.php?rid=855310&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D137 Fibroids, also known as myoma or leiomyomata, are common benign growths of the uterine musculature which cause irregular and painful periods, bloating and lower abdominal pain, and can affect fertility. Uterine fibroids are extremely common. More than 75% of women can be found to have small fibroids using MRI, although only about 30% of all women will have fibroids large enough to be noted during a pelvic exam, and the vast majority of even these women will never have symptoms and will never require treatment. For the rare patient who does have problems, there are a number of sound and effective options available including laparoscopy or laparotomy. Hysterectomy should be performed only in patients with symptomatic disease. TAP and Schering AG are codeveloping asoprisnil (J867), t... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855310 Mon, 10 Sep 2007 01:39:34 +0100 855310 http://www.medworm.com/index.php?rid=855309&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D138 Blood transfusions are widely used to treat patients with chronic disorders such as sickle cell disease, beta-thalassemia and anemia. Because red blood cells contain iron, and there is no natural way for the body to eliminate it, patients who receive repeated blood transfusions can accumulate iron in the body until it reaches toxic levels. It is important to remove excess iron from the body, because it can gather in the heart, liver, and other organs and may lead to organ damage. Although treatments are available to eliminate iron overload, these are all accompanied by side effects and/or drawbacks, which makes the development of improved new chelating agents for the treatment of iron overload more urgent. Novartis has filed regulatory submissions for Exjade® (deferasirox, ICL-670), t... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855309 Mon, 10 Sep 2007 01:39:34 +0100 855309 http://www.medworm.com/index.php?rid=855308&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D139 Schizophrenia is a severe disabling and chronic form of psychosis that develops in approximately 1% of the population. Schizophrenia is characterized by positive, negative, affective and cognitive symptoms. Positive symptoms comprise, among others, delusions and hallucinations. The negative symptoms include social withdrawal, blunted affects and diminished capacity of speech. Affective symptoms are mainly depression and anxiety. Typical cognitive deficits are impaired attention and memory and some times disorganized speech. While most widely used treatments may be effective in controlling acute symptoms of schizophrenia, they are all associated with a variety of side effects that negatively influence their usefulness in long-term treatment. New treatments that improve symptomatology bu... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855308 Mon, 10 Sep 2007 01:39:34 +0100 855308 http://www.medworm.com/index.php?rid=855307&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D140 Gap junction modulation is a promising and completely novel mechanism of action for the treatment of cardiovascular disorders. Gap junctions are a class of protein channels that are responsible for conducting electrical impulses between cells in the heart to maintain normal rhythm. Rotigaptide (ZP-123, GAP-486), a stable antiarrhythmic peptide analogue that has been shown to increase gap junction intercellular conductance in cardiomyocytes, is currently under clinical investigation by Wyeth for the treatment of arrhythmias. This novel compound was the subject of presentations at two recent conferences. The mechanism of action of rotigaptide and preclinical study results were presented at the International Gap Junction Conference in Whistler, British Columbia in August. Rotigaptide increa... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855307 Mon, 10 Sep 2007 01:39:34 +0100 855307 http://www.medworm.com/index.php?rid=855306&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D141 WHO’s Pandemic Preparedness Plan recommends that countries stockpile the antiviral drugs oseltamivir and zanamivir The H5N1 strain of influenza A, first detected in South Africa in 1961, has spread rapidly throughout avian species since 1997, when it first became a health concern in Hong Kong. Although transmission from birds to humans is rare, it is a cause for serious concern due to the extremely high mortality associated with human H5N1 disease. According to the World Health Organization (consulted October 27, 2005), to date the virus has infected 121 people worldwide, killing 62 of them. Although human-to-human transmission has yet to be established, health officials are on high alert worldwide in the face of a potential influenza pandemic caused by this highly deadly virus. Such a ... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855306 Mon, 10 Sep 2007 01:39:34 +0100 855306 http://www.medworm.com/index.php?rid=855305&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D142 The European Medicines Agency (EMEA) has granted marketing authorization in 27 European countries for Servier's Ivabradine hydrochloride (Procoralan®), the first selective and specific I(f) inhibitor, for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers. Ivabradine, discovered and developed by Servier, is the first pure heart rate-lowering agent and acts by selective inhibition of the cardiac pacemaker I(f) current, which controls spontaneous diastolic depolarization in the sinus node and regulates heart rate. Ivabradine's effects are selective to the sinus node; it has no effect on intracardiac conduction, myocardial contractility or ventricular repolarization. Unlike beta-block... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855305 Mon, 10 Sep 2007 01:39:34 +0100 855305 http://www.medworm.com/index.php?rid=855304&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D143 (Alzhemed™) is an antiamyloidogenic agent from Neurochem that is in phase III trials for the oral treatment of mild to moderate Alzheimer's type dementia and in phase II trials (as Cerebril™) for the treatment of hemorrhagic stroke due to cerebral amyloid angiopathy (CAA). If ongoing clinical trials are successful, tramiprosate could become the first in a new class of orally available therapeutics developed to stop the progression of Alzheimer’s disease (AD). Phase II results demonstrated that the drug produced no apparent safety concerns and was well tolerated in individuals with mild to moderate AD. In the context of Alzheimer's disease, the disease-modifying drug candidate is thought to act by preventing and slowing the formation and the deposition of amyloid fibrils in... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855304 Mon, 10 Sep 2007 01:39:34 +0100 855304 http://www.medworm.com/index.php?rid=855303&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D144 Last December the U.S. FDA approved the novel oncolytic drug sorafenib (Nexavar®) for the treatment of patients with advanced renal cell carcinoma. Codeveloped by Bayer and Onyx, sorafenib is the first, oral multikinase inhibitor that targets serine/threonine and receptor tyrosine kinases in both the tumor cell and tumor vasculature. In preclinical models, the drug targeted members of two classes of kinases known to be involved in both tumor cell proliferation and tumor angiogenesis. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-beta, KIT and FLT-3. The companies made the drug available to patients within 24 hours of approval. The FDA approved sorafenib based on data from the largest ever randomized, placebo-controlled, international trial in patients with advanced renal... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855303 Mon, 10 Sep 2007 01:39:34 +0100 855303 http://www.medworm.com/index.php?rid=855302&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D145 Nicotine addiction is one of the most prevalent addictive behaviors worldwide. According to the World Health Organization, 1.3 billion men, women and children worldwide are smokers. In spite of increased awareness and action on the part of both governments and individuals, tobacco continues to be the leading cause of preventable disease and death in the U.S., as well as many other countries. According to WHO, there are nearly 5 million tobacco-related deaths worldwide each year and nearly half of the smokers in the world today will die as a cause of their addiction. Although the development of pharmacotherapies for nicotine addiction has traditionally centered on nicotine replacement, more recent discoveries have led to a new line of research into non-nicotine therapies, including the an... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855302 Mon, 10 Sep 2007 01:39:34 +0100 855302 http://www.medworm.com/index.php?rid=855301&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D146 The naturally occurring incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are potent insulinotropic hormones which are vital in the control of glucose homeostasis. GLP-1 stimulates the body's ability to produce insulin in response to raised blood glucose levels, inhibits the release of glucagon following meals and slows the rate of nutrient absorption into the bloodstream. The development of type 2 diabetes may be slowed, or even prevented, by extending the duration of action of endogenous GLP-1. The serine protease dipeptidyl-peptidase IV (DPP-IV) inactivates GLP-1, and acts as a catalyst in the processes of signal transduction during the immune response leading to the development of type 2 diabetes. By preserving GLP-1 levels, DPP-IV inhibition st... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855301 Mon, 10 Sep 2007 01:39:34 +0100 855301 http://www.medworm.com/index.php?rid=855300&cid=s_36111_59_f&fid=36111&url=http%3A%2F%2Fwww.prous.com%2Fmolecules%2Fdefault.asp%3FID%3D147 is an orally-active small molecule inhibitor of dipeptidyl peptidases, such as fibroblast activation protein (FAP), found in the stroma of epithelial tumors. Inhibition of these proteins results in the inhibition of the growth of certain malignant tumors. Talabostat also stimulates a variety of cytokines and chemokines, which provide upregulation of both innate and acquired immune systems, thereby accelerating the reconstitution of the hematopoietic system. In October 2005, originator Point Therapeutics initiated the phase III program for talabostat in metastatic non-small cell lung cancer (NSCLC). The program will evaluate talabostat in patients with stage IIIB/IV NSCLC after failure of a platinum-based chemotherapy. Two randomized, double-blind, placebo-controlled trials will enroll up... Prous Science - Molecule of the Month info http://www.medworm.com/rss/comments.php?id=855300 Mon, 10 Sep 2007 01:39:34 +0100 855300