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.
Many roots of organic chemistry, and of medicinal chemistry in particular, often originate in what might seem like an unlikely place: the dyestuff industry of the late 19th century. I had already known this to some degree, but writing the historical vignettes in The Chemistry Book really brought it home to me. And if you… Read More
Well, since I mentioned just the other day (and not for the first time) that determining drug concentrations and localization in cells is a major unsolved problem, I should probably talk about this new paper (a collaboration between groups in Edinburgh and Glasgow, nice to see since their cities are not always collaborative in all… Read More
I will cause no controversy by saying that most of the small-molecule compounds that we develop as potential drugs in this business are rather poorly soluble in water. Every organization I’ve worked in has made the standard jokes about “brick dust” and “powdered Teflon”, and for the well-founded standard reasons. A lot… Read More
Assigning enantiomers (mirror-image isomers of a compound, for the non-organic-chemists in the crowd) can be a pain. By definition, no non-chiral technique can tell the difference between such things, and many of the chiral techniques will just tell you that they’re different, but not which one is which. Take, for example, chiral chromatograp… 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
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
Let’s think for a minute about what’s going on with tiny particles in solution, because we chemists spend an awful lot of time dealing with those. These particles vary in size from individual atoms all the way through small molecules, larger biomolecules and polymers, nanoscale engineered particles, micronized powders, etc., but the goo… Read More
Catalytically active proteins come in many varieties, and you can classify them in many ways. When you look closely at their structures, one such scheme might be the “solid” ones versus the “delicately balanced” ones. In the first category would be things like carbonic anhydrase or acetylcholinesterase: they do their jobs mo… Read More
Here’s another for the “things we just didn’t realize” file. This article is a nice look at “miniproteins” (also known as micropeptides), small but extremely important species that we’ve mostly missed out on due to both our equipment and our own biases in looking at the data. Other recent overviews are here… Read More
Kekulene! This is one of those molecules that someone who’s learning organic chemistry might sketch out on a whiteboard, wondering if it really exists. It does, but it’s not like we have a lot of recent information about it. There was a preparation of it in 1978 (from the Staab group at the Max-Planck Institute… Read More
