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.
DNA-encoded libraries are a technique that many in the field should be familiar with, and they’ve come up many times here on the blog. The basic idea is simple: you build up a set of small molecules with some relatively simple synthetic steps, with plenty of branching at each stage. As a thought experiment, this… Read More
Among the many drug-discovery lessons that this pandemic is highlighting is the difficulty of meeting the challenges of a new target, a new pathogen, a new disease, or a new mechanism of action. When you look at the history of the drug industry, the typical time for an effective therapy to be developed from a… Read More
One of the notable things about the current pandemic is the way that all our modern biology and analytical techniques are on display. Molecular biology, structural biology, bioinformatics, technologies like cryo-EM structure determination, fast sequencing, protein interaction screening and more – this is a real-time look at how basic biomedic… Read More
Time for a word about screening for new coronavirus drugs. Things have gone on long enough for quite a few groups to produce supplies of the various viral proteins and set up small-molecule screens against them. That’s no bad thing in itself, although it is a slow thing, a very slow thing by the standards… Read More
There’s a lot of news to catch up on, and to keep things straight I’ll divide the hydroxychloroquine part out into this post, and cover others in the next one. My previous reviews of the clinical data in this area are here. First up is this study from France. It’s another very small one, and… Read More
I wanted to mention this paper, which is one of the more comprehensive ones on the idea of repurposing existing drugs against the coronavirus. It’s a large multicenter team that clearly did a lot of very fast coordination to produce these results. What they’ve done is looked at the complete suite of proteins produced by… 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
At a previous company some years back, I was interested in getting a “covalent fragment” collection going, and did to a small extent. It got screened against some antibacterial targets, but never became all that popular. That was partly because fragment-based screening was a younger field, and combining it with covalent drug discovery … Read More
I remember the time before anyone did fragment-based drug discovery, when I heard high-micromolar binding ligands described as “carpet lint” or “stuff from the bottom of your shoe”. And you only heard then when the assays themselves even read out at that level, which certainly wasn’t a given. When I started, a suggesti… Read More
This new paper shows one reason why it’s so tricky to calculate compound binding in an active site (which is what we’d want to do in order to do effective in silico virtual screening). The authors (a multicenter team from York, Demuris, Vernalis, and St. Jude) are looking at a virulence protein from H. influenzae… Read More
