Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
When you look closely at cellular biochemistry, what you see are a lot of amazing processes that are surrounded by amazing amounts of redundancy, backups, patches, and accumulated tweaks and fixes. That’s evolution for you; these things have been piling up for a billion years or two, and we’re all the descendants of the critters… Read More
The FAAH (fatty acid amide hydrolase) enzyme system has provided a number of headlines over the years. FAAH itself is involved in the brain’s endocannabinoid system – it clears neurotransmitters like anandamide – and a number of other biologically important hydroxyethylamide and acyltaurines. So the potential for inhibitors of it… Read More
Venetoclax (ABT-199) is an unusual drug. But now there’s some unusually bad (and unexpected) news about it. That’s the structure at right, and medicinal chemists will understand immediately why it’s a bit of an outlier. With a molecular weight of 868, that structure just keeps on going, with a somefeatures that you donR… Read More
A few years ago on this blog, I wrote several times about a small company called Zafgen and their unusual epoxide-based chemical matter (beloranib) that was in development for the rare Prader-Willi syndrome. That’s a genetic disorder that includes, among many other problems, constant hunger (with the complications that you’d expect fro… Read More
The proteasome is quite the structure. It is the shredding unit of the cell, where no-longer-needed proteins go to be ripped down to their components for recycling, and it’s become a more and more important part of drug discovery over the years. For one thing, all this fashionable targeted protein degradation work is about sending… Read More
There have been some pretty dramatic clinical trial results coming out recently, and unfortunately drama is a variable that can take either a positive or a negative sign in front of it. On the plus side, MacroGenix, a company that not many people had been paying attention to, announced results of a head-to-head trial of… Read More
Here’s a caution from a new paper out of Manchester. The group had been synthesizing inhibitors of PARG (poly-ADP ribose glycohydrolase), an enzyme involved in DNA repair. The general chemotype is shown at right, but there are a number of variations. That fluorine is a new addition, though. The corresponding cyclopropylmethyl se… Read More
There’s a chemical contamination story in the generic drug industry that just isn’t going away. Late last summer, some lots of valsartan were recalled due to detection of N-nitrosodimethylamine (NDMA), and the problem has just continued since then. We’ll get into the chemistry of this problem in a minute, but first off, looking at… Read More
3-bromopyruvate is an interesting and controversial compound. It’s been reported to be an active chemotherapy agent, apparently acting via covalent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequent metabolic effects via loss of pyruvate itself. Several years ago, you could come across numerous web pages touting it… Read More
There have been some potentially significant developments in Parkinson’s disease, which is a good thing to be able to report. As populations age around the world, PD has been on its way up, but therapies for it have not been, despite a good deal of work in the field. But it looks like some clues… Read More
