Allergan Twists and Turns
It's getting nasty over at Allergan. They're still trying to fight off a takeover attempt by Valeant, making the case that the company's R&D efforts are not a waste of money (which, only slightly simplified, is the Valeant position regarding every company they're taking over).
But Allergan's had a lot of trouble getting one of their drugs (Semprana) through the FDA. Semprana is an inhaled version of the classic dihydroergotamine therapy for migraine, and had been rejected last year when it was still known as Levadex. The recent further delay isn't helping Allergan make its case, and Valeant is using this news to peel off...
Source: In the Pipeline - July 21, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs
Chemistry Class For the "Food Babe"?
I found this article from the Charlotte Observer on the "Food Babe" (Vani Hari) very interesting. A "menu consultant" for Chick-Fil-A, is she? Who knew?
I've come across a horribly long string of chemistry misapprehensions, mistakes, and blunders while looking at her site - she truly appears to know nothing whatsoever about chemistry, not that this would appear to bother her much. (Wavefunction has a good article on these). I noticed in the comments section of the newspaper's article that someone is apparently trying to crowdsource a fundraising drive to send her to some chemistry classes. I enjoy that idea very much, alt...
Source: In the Pipeline - July 18, 2014 Category: Chemists Tags: General Scientific News Source Type: blogs
Thalidomide, Bound to Its Target
There's a new report in the literature on the mechanism of thalidomide, so I thought I'd spend some time talking about the compound. Just mentioning the name to anyone familiar with its history is enough to bring on a shiver. The compound, administered as a sedative/morning sickness remedy to pregnant women in the 1950s and early 1960s, famously brought on a wave of severe birth defects. There's a lot of confusion about this event in the popular literature, though - some people don't even realize that the drug was never approved in the US, although this was a famous save by the (then much smaller) FDA and especially by Fra...
Source: In the Pipeline - July 18, 2014 Category: Chemists Tags: Biological News Source Type: blogs
TDP-43 and Alzheimer's
There are quite a few headlines today about a link between Alzheimer's and a protein called TDP-43. This is interesting stuff, but like everything else in the neurodegeneration field, it's going to be tough to unravel what's going on. This latest work, just presented at a conference in Copenhagen, found (in a large post mortem brain study of people with diagnosed Alzheimer's pathology) that aberrant forms of the protein seem to be strongly correlated with shrinkage of the hippocampus and accompanying memory loss.
80% of the cohort with normal TDP-43 (but still showing Alzheimer's histology) had cognitive impairment at dea...
Source: In the Pipeline - July 17, 2014 Category: Chemists Tags: Alzheimer ' s Disease Source Type: blogs
Google's Big Data Flu Flop
This article in Science finds that the real-world predictive power has been pretty unimpressive. And the reasons behind this failure are not hard to understand, nor were they hard to predict. Anyone who's ever worked with clinical trial data will see this one coming:
The initial version of GFT was a particularly problematic marriage of big and small data. Essentially, the methodology was to find the best matches among 50 million search terms to fit 1152 data points. The odds of finding search terms that match the propensity of the flu but are structurally unrelated, and so do not predict the future, were quite high. GFT d...
Source: In the Pipeline - March 24, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs
Nitrogen Heterocycles Ahoy
Here's the sort of review that every working medicinal chemist will want to take a look at: Jeffrey Bode and graduate student Cam-Van T. Vo are looking at recent methods to prepare saturated nitrogen heterocycles. If you do drug discovery, odds are that you've worked with more piperidines, pyrrolidines, piperazines, morpholines, etc. than sticks can be shaken at. New ways to make substituted variations on these are always welcome, and it's good to see the latest work brought together into one place.
There's still an awful lot to do in this area, though. As the review mentions, a great many methods rely on nitrogen protect...
Source: In the Pipeline - March 24, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
Ezetimibe In the Marketplace
Several years ago, the Schering-Plough cholesterol absorption inhibitor (Zetia, ezetimibe) and its combination pill with simvastatin (Vytorin) were the subject of a lot of puzzled controversy. A clinical trial (ENHANCE) looking at arterial wall thickness in patients with familial hypercholesteremia had unexpectedly shown little or no benefit, although statins themselves had worked in this population. This led to plenty of (still unresolved) speculation about the drug's mechanism of action, whether it really was going to be of benefit to the wider patient population, what this meant for the surrogate endpoint of LDL lowerin...
Source: In the Pipeline - March 24, 2014 Category: Chemists Tags: Cardiovascular Disease Source Type: blogs
Dosing by Body Surface Area
We were talking about allometry around here the other day, which prompts me to mention this paper. It used the reports of resveratrol dosing in animals, crudely extrapolated to humans, to argue that the body surface area normalization (BSA) method was a superior technique for dose estimation across species.
Over the years, though, the BSA method has taken some flak in the literature. It's most widely used in oncology, especially with cytotoxics, but there have been calls to move away from the practice, calling it a relic with little scientific foundation. (The rise of a very obese patient population has also led to contro...
Source: In the Pipeline - March 21, 2014 Category: Chemists Tags: Pharmacokinetics Source Type: blogs
Another Use for Xenon
An Australian reader sends this along from The Economist. Apparently xenon has been used for several years now to enhance athletic performance - who knew? Well, athletes, for one - here's an Australian cycling magazine talking about it, and Russian athletic federations have been recommending it for some time. That cycling article has a copy of a letter from the Russian Olympic committee, thanking a supplier for providing xenon to help prepare the team for the 2006 winter games in Turin.
One's first impulse would be to snort and say "Snake oil!", but one's first impulse would probably be wrong. Xenon exposure is known to s...
Source: In the Pipeline - March 21, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
For Some Folks, It's New Year's Day
A quick "eid-e shoma mubarak" to all those out there who are celebrating Norouz, the spring-equinox version of New Year's Day. My Iranian wife certainly is, and I will be pitching in by consuming large amounts of the home-made sweets that her mother has produced, and by frying a large quantity of fish for a big meal later on. For once, there's actually some blue sky and sunshine out there today (albeit with heaps of melting snow everywhere). But it sure beats a faceful of sleet, which has been the case several times in years past. (If you've ever seen the old W. C. Fields short, "The Fatal Glass of Beer", you'll get the id...
Source: In the Pipeline - March 20, 2014 Category: Chemists Tags: Blog Housekeeping Source Type: blogs
Small Molecule Chemistry's "Limited Utility"?
Over at LifeSciVC, guest blogger Jonathan Montagu talks about small molecules in drug discovery, and how we might move beyond them. Many of the themes he hits have come up around here, understandably - figuring why (and how) some huge molecules manage to have good PK properties, exploiting "natural-product-like" chemical space (again, if we can figure out a good way to do that), working with unusual mechanisms (allosteric sites, covalent inhibitors and probes), and so on. Well worth a read, even if he's more sanguine about structure-based drug discovery than I am. Most people are, come to think of it.
His take is very sim...
Source: In the Pipeline - March 20, 2014 Category: Chemists Tags: Drug Industry History Source Type: blogs
Years Worth of the Stuff
This time last year I mentioned a particularly disturbing-looking compound, sold commercially as a so-called "selective inhibitor" of two deubiquitinase enzymes. Now, I have a fairly open mind about chemical structures, but that thing is horrible, and if it's really selective for just those two proteins, then I'm off to truck-driving school just like Mom always wanted.
Here's an enlightening look through the literature at this whole class of compound, which has appeared again and again. The trail seems to go back to this 2001 paper in Biochemistry. By 2003, you see similar motifs showing up as putative anticancer agents i...
Source: In the Pipeline - March 20, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs
Another Whack at the Stem Shortage Myth
Over at The Atlantic, Michael Teitelbaum has another crack at demolishing the "STEM shortage" myth. Looking over actual employment data, he finds:
All have concluded that U.S. higher education produces far more science and engineering graduates annually than there are S&E job openings—the only disagreement is whether it is 100 percent or 200 percent more. Were there to be a genuine shortage at present, there would be evidence of employers raising wage offers to attract the scientists and engineers they want. But the evidence points in the other direction: Most studies report that real wages in many—but not all—scien...
Source: In the Pipeline - March 19, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs
More Things Synthetic Chemists Hate
I enjoyed this post over at Synthetic Remarks on "Five things synthetic chemists hate". And I agree; I hate all of 'em, too. Allow me to add a few to the list:
1. The Mysterious Starting Material. How many times have you looked through an experimental section only to see a synthesis start cold, from a non-commercial compound whose preparation isn't given, or even referenced? One that doesn't seem to have any foundation anywhere else in the literature, either? I think that this is a bit more common in the older literature, but it shouldn't be happening anywhere.
2. It Works on Benzaldehyde; What More Do You Want? What abo...
Source: In the Pipeline - March 19, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
Another DNA-Barcoded Program From GSK
Two more papers have emerged from GSK using their DNA-encoded library platform. I'm always interested to see how this might be working out. One paper is on compounds for the tuberculosis target InhA, and the other is aimed at a lymphocyte protein-protein target, LFA-1. (I've written about this sort of thing previously here, here, and here).
Both of these have some interesting points - I'll cover the LFA-1 work in another post, though. InhA, for its part, is the target of the well-known tuberculosis drug isoniazid, and it has had (as you'd imagine) a good amount of attention over the years, especially since it's not the cl...
Source: In the Pipeline - March 18, 2014 Category: Chemists Tags: Infectious Diseases Source Type: blogs
