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.
I mentioned polymorphs the other day, and no mention of those should go by without a reference to the classic 1995 article on “disappearing polymorphs” and its 2015 follow-up. This is a controversial area, but what everyone can agree on is that there are numerous cases where some particular crystal form of a compound has… Read More
Anyone who’s done fragment-based drug design (especially) or who has just looked at a lot of X-ray crystal structures of bound ligands will be able to back up this statement: if you sit down with a series of such structures, all bound to the same site, it is very, very difficult to rank-order them in… Read More
Chemists have a familiarity with many elements and many compounds, from having worked with them or studied them in the literature. You get a feel for what’s “normal” and for what’s unusual, and there are quite a few degrees of the latter. Take compounds of bromine, for example. Most any working chemist will immediately recog… Read More
Here’s a very useful article in JAMA on how to read an article that uses machine learning to propose a diagnostic model. It’s especially good for that topic, but it’s also worth going over for the rest of us who may not be diagnosing patients but who would like to evaluate new papers that claim… Read More
This is not going to be a reassuring story – not for the biomedical literature, and not for the Chinese scientific establishment. But the head of the official Research Integrity initiative there, Xuetao Cao, a former head of the Chinese Academy of Medical Sciences and current president of Nankai University, is now thoroughly involved in… Read More
There are a lot of things in human medicine that make sense broadly, but not in detail. We understand why a thing could happen, but not exactly how it happens. A case in point in alcoholic liver disease. It makes perfect sense that longterm alcohol abuse would damage the liver – it’s the front line… Read More
Here’s a surprise: a report of a completely new (and rather unusual) allotrope of carbon. There doesn’t appear to be a manuscript out there yet, but the results were presented earlier this month at a conference in Richmond and earlier this year at the APS meeting, and caused a stir. Weirdly, this one appears to… Read More
We’re seeing a lot of bivalent molecules in drug discovery these days, especially with the popularity of bifunctional protein degrader ligands. The general structure of such thing is (ligand)—-linker—-(ligand), with the two ligands chosen (in the case of targeted protein degradation) to bring a ubiquitin ligase complex up close to… Read More
Roald Hoffmann and Jean-Paul Malrieu have a three-part essay out in Angewandte Chemie on artificial intelligence and machine learning in chemistry research, and I have to say, I’m enjoying it more than I thought I would. I cast no aspersion against the authors (!) – it’s just that long thinkpieces from eminent scientists, especial… Read More
If you’re a chemist, then you like crystallization. I think that’s pretty much a given; I’ve never met anyone who doesn’t appreciate a good crystal, and watching them form out of a solution never stops feeling a bit like magic. When I was doing a project involving metal-organic frameworks, I had some of the best… Read More
