A Last Summer Day Off
I'm going to be taking an extra day of vacation before the kids start back to school, so I'm adding to the Labor Day weekend today. Blogging will resume on Tuesday, unless something gigantic happens before then. If I can come up with something appropriate, maybe I'll put up a recipe! (Source: In the Pipeline)
Source: In the Pipeline - August 29, 2014 Category: Chemists Tags: Blog Housekeeping Source Type: blogs
The Early FDA
Here's a short video history of the FDA, courtesy of BioCentury TV. The early days, especially Harvey Wiley and the "Poison Squad", are truly wild and alarming by today's standards. But then, the products that were on the market back then were pretty alarming, too. . . (Source: In the Pipeline)
Source: In the Pipeline - August 28, 2014 Category: Chemists Tags: Regulatory Affairs Source Type: blogs
Drug Repurposing
A reader has sent along the question: "Have any repurposed drugs actually been approved for their new indication?" And initially, I thought, confidently but rather blankly, "Well, certainly, there's. . . and. . .hmm", but then the biggest example hit me: thalidomide. It was, infamously, a sedative and remedy for morning sickness in its original tragic incarnation, but came back into use first for leprosy and then for multiple myeloma. The discovery of its efficacy in leprosy, specifically erythema nodosum laprosum, was a complete and total accident, it should be noted - the story is told in the book Dark Remedy. A physicia...
Source: In the Pipeline - August 28, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs
The Smallest Drugs
Here is the updated version of the "smallest drugs" collection that I did the other day. Here are the criteria I used: the molecular weight cutoff was set, arbitrarily, at aspirin's 180. I excluded the inhaled anaesthetics, only allowing things that are oils or solids in their form of use. As a small-molecule organic chemist, I only allowed organic compounds - lithium and so on are for another category. And the hardest one was "Must be in current use across several countries". That's another arbitrary cutoff, but it excludes pemoline (176), for example, which has basically been removed from the market. It also gets rid of ...
Source: In the Pipeline - August 27, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
Life Is Too Short For Some Journal Feeds
What scientific journals can you not be bothered to keep up with? I know, sometimes it's tempting to answer "all of them", but a well-informed chemist really should watch what comes out in the better ones. But how about the not-so-better ones? The "Life's too short" ones? Reading journals by RSS gives a person some perspective on signal-to-noise.
One problem is that Elsevier's RSS feeds are sort of perpetually hosed. Are they working now? I haven't checked in a while, because I finally gave up on them. And that means that I don't regularly look at Tetrahedron Letters or Bioorganic and Medicinal Chemistry Letters, even th...
Source: In the Pipeline - August 27, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs
A New Look at Phenotypic Screening
There have been several analyses that have suggested that phenotypic drug discovery was unusually effective in delivering "first in class" drugs. Now comes a reworking of that question, and these authors (Jörg Eder, Richard Sedrani, and Christian Wiesmann of Novartis) find plenty of room to question that conclusion.
What they've done is to deliberately focus on the first-in-class drug approvals from 1999 to 2013, and take a detailed look at their origins. There have been 113 such drugs, and they find that 78 of them (45 small molecules and 33 biologics) come from target-based approaches, and 35 from "systems-based" appro...
Source: In the Pipeline - August 26, 2014 Category: Chemists Tags: Drug Assays Source Type: blogs
Small Molecules - Really, Really Small
Mentioning such a small compound as pirfenidone prompts me to put up the graphic shown below: these are the smallest commonly used drugs that I can think of. (OK, there's cocaine as a nasal anaesthetic - no, really - but that's where I draw the line at "commonly used". Nominations for ones that I've missed are welcome, and I'll update the list as needed. Note: four more have been added since the initial post, with more to come. This sort of thing really makes a chemist think, though - some of these compounds are very good indeed at what they do, and have been wildly successful. We need to keep an open mind about small mole...
Source: In the Pipeline - August 25, 2014 Category: Chemists Tags: Drug Industry History Source Type: blogs
InterMune Bought
It has been a bizarre ride for InterMune, its employees, and its investors. But now it ends with Roche buying them for $8.3 billion dollars, a sum that would have brought incredulous stares a few years ago. The deal makes sense for Roche, and it will provide investors a rationale for years as they buy into small biopharma companies - trying to pick the next InterMune, you know. (Source: In the Pipeline)
Source: In the Pipeline - August 25, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs
Citable Garbage
Experimental and Clinical Cardiology used to be a reputable journal. Now it's a trash heap piled with crap. No, literally - the Ottawa Citizen newspaper has proof, thanks to reporter Tom Spears (who's an experienced hand at this). The journal was sold last year, and the new owners will publish absolutely anything you send them, as long as you send them $1200 to their bank account in the Turks and Caicos Islands. I wish I were making all that up, but that is exactly how it goes, offshore banking and all.
Spears whipped together a gibberish cardiology paper by taking one about HIV and doing a find-and-replace to substitute ...
Source: In the Pipeline - August 25, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs
The Palbociclib Saga: Or Why We Need a Lot of Drug Companies
Science has an article by journalist Ken Garber on palbociclib, the Pfizer CDK4 compound that came up here the other day when we were discussing their oncology portfolio. You can read up on the details of how the compound was put in the fridge for several years, only to finally emerge as one of the company's better prospects. The roots of the project go back to about 1995 at Parke-Davis:
Because the many CDK family members are almost identical, “creating a truly selective CDK4 inhibitor was very difficult,” says former Parke-Davis biochemist Dave Fry, who co-chaired the project with chemist Peter Toogood. “A lot of ...
Source: In the Pipeline - August 22, 2014 Category: Chemists Tags: Cancer Source Type: blogs
Why Not Bromine?
So here's a question for the medicinal chemists: how come we don't like bromoaromatics so much? I know I don't, but I have trouble putting my finger on just why. I know that there's a ligand efficiency argument to be made against them - all that weight, for one atom - but there are times when a bromine seems to be just the thing. There certainly are such structures in marketed drugs. Some of the bad feelings around them might linger from the sense that it's sort of unnatural element, as opposed to chlorine, which in the form of chloride is everywhere in living systems.
But bromide? Well, for what it's worth, there's a rep...
Source: In the Pipeline - August 21, 2014 Category: Chemists Tags: Drug Development Source Type: blogs
Fragonomics, Eh?
Edward Zartler ("Teddy Z" of the Practical Fragments blog) has a short piece in the latest ACS Medicinal Chemistry Letters on fragment-based drug discovery. He applies the term "fragonomics" to the field (more on this in a moment), and provides a really useful overview of how it should work.
One of his big points is that fragment work isn't so much about using smaller-than-usual molecules, as it is using molecules that make only good interactions with the target.. It's just that smaller molecules are far more likely to achieve that - a larger one will have some really strong interactions, along with some things that actua...
Source: In the Pipeline - August 21, 2014 Category: Chemists Tags: Drug Assays Source Type: blogs
Amicus Fights Its Way Through in Fabry's
Perseverance is a critical variable in drug discovery. Too little of it, and you are absolutely guaranteed to fail - no drug has ever made it to market without trying the patience of everyone involved. Too much of it, and you are very nearly guaranteed to waste all your money: most drug development projects don't work, and eventually reach a point where no amount of time or money could make them work, either. Many are the efforts where leaders have gritted their teeth, redoubled their efforts, and led everyone further into the abyss.
But sometimes these things come through, and that's what seems to have happened with Amic...
Source: In the Pipeline - August 20, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs
Did Pfizer Cut Back Some of Its Best Compounds?
John LaMattina has a look at Pfizer's oncology portfolio, and what their relentless budget-cutting has been doing to it. The company is taking some criticism for having outlicensed two compounds (tremelimumab to AstraZeneca and neratinib to Puma) which seem to be performing very well after Pfizer ditched them. Here's LaMattina (a former Pfizer R&D head, for those who don't know):
Unfortunately, over 15 years of mergers and severe budget cuts, Pfizer has not been able to prosecute all of the compounds in its portfolio. Instead, it has had to make choices on which experimental medicines to keep and which to set aside. Howev...
Source: In the Pipeline - August 20, 2014 Category: Chemists Tags: Cancer Source Type: blogs
Don't Optimize Your Plasma Protein Binding
Here's a very good review article in J. Med. Chem. on the topic of protein binding. For those outside the field, that's the phenomenon of drug compounds getting into the bloodstream and then sticking to one or more blood proteins. Human serum albumin (HSA) is a big player here - it's a very abundant blood protein that's practically honeycombed with binding sites - but there are several others. The authors (from Genentech) take on the disagreements about whether low plasma protein binding is a good property for drug development (and conversely, whether high protein binding is a warning flag). The short answer, according to ...
Source: In the Pipeline - August 19, 2014 Category: Chemists Tags: Pharmacokinetics Source Type: blogs
