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.
Plenty of people know that there’s a gas given off by ripe fruit that can itself accelerate ripening in others – the “banana in a bag” technique. That gas is of course ethylene, identified as such in plants in the early 20th century, and the more chemistry you know, the odder it seems that it… Read More
Word has been spreading rapidly about this preprint on Chemrxiv.org, from a joint UCLA/Caltech team. It details the use of the cryo-electron microscopy technique called micro-electron diffraction (MicroED) for the structure determination of small molecules, and it’s absolutely startling. I read it last night, with many exclamations along the… Read More
I really enjoyed this paper from Merck’s Process R&D group, but some readers will be saying “Yeah, but that’s just because you really enjoy photochemistry reactions”. The latter part is true, but it’s the sort of paper that we need to help drain some of the voodoo out of all the exciting photochemistry work that… Read More
There are a lot of topics that we really should know more about in drug discovery, but which are buried inside projects inside particular organizations. Some of this knowledge is available once you’re inside said organization, but some of it is hard to assemble even then (much less into a review from outside). An example… Read More
This paper is really a tour de force of analytical chemistry, because it does something that I didn’t think was possible. The team is looking at a rather ancient creature, Dickinsonia. In fact, you could argue that it’s the ancient creature, since it’s one of the Ediacaran organisms that are part of the first explosion… Read More
OK, all this cryo-electron microscopy stuff is great, new protein structures, things that are huge, that can’t be crystallized, fine, fine: but when, the medicinal chemists in the audience ask, will we be able to use it for structure-based drug discovery? This new review tries to answer just that question. The first thing that you… Read More
If you’ve ever been around an X-ray crystallography setup, one of the constants is a tube directing a blast of chilly vapor at the crystal that’s mounted for analysis. It’s usually a stream of cold nitrogen gas, often set up as a blast of the cold stuff surrounded by a second concentric layer of dry… Read More
There are plenty of things to optimize in a med-chem project other than binding affinity. But if you don’t have at least some level of binding, you may not have a med-chem project. And while from the outside, you might think that understanding how and why compound A binds to a given target while compound… Read More
Let us pause to consider the weirdness of diamond. Not because diamonds are rare – they’re not, at least compared to many other minerals and gemstones. But diamond itself has very unusual physical properties, and that comes down to its structure. As is well known to chemists, it’s a three-dimensional lattice of bonded sp3 carbons… Read More
Medicinal chemists are extremely familiar with G-protein coupled receptors (GPCRs), and it’s a safe bet that any pretty much any neurotransmitter (for example) that can be named by the general public is a GPCR ligand, too. Serotonin, dopamine, histamine – all the classics are there, and that’s reflected in the number of marketed d… Read More
