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.
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
With all the work going into targeted protein degradation now (recent review), we’re discovering a lot of things about it that weren’t apparent at first. To pick an obvious one, these things have several steps in their mechanism (binding to the target protein, binding to a ubiquitin ligase to form a ternary complex, ubiquitination of… Read More
I wanted to mention this paper that’s out in Nature, especially since I was mentioning azide/alkyne click chemistry the other day. If you’re using that system in any sort of chemical diversity sense, you’ve run into problems on the azide end. There are not a whole lot of commercially available azides out there (although definitely… Read More
Layer upon layer! That’s what cell biology provides you with – just when you think you understand some area of it, things turn out to be more complex. I’m going on in this mode after looking over this new preprint from the Bertozzi lab at Stanford, which uncovers a new class of biomolecules that no… Read More
In case you don’t know, there’s officially an effort to try to develop chemical probes for basically every protein in the human proteome. The “Target 2035” initiative has been looking through the literature and finding what you’d expect: power-law distributions that have most people working on proteins that other peopl… Read More
Just how are things organized in a living cell? What’s next to what, in three dimensions? That is, of course, a really hard question to answer, but we’re going to have to be able to answer it in a lot of contexts (and at high resolution) if we’re ever going to understand what’s going on… Read More
The need for good chemical probes continues, and (sadly) so does the use of crappy ones. That’s what I took away from this recent paper from a multicenter team out of London. They’re looking at commonly used probes for inhibition of N-myristoyltransferase (NMT) enzymes, and it’s one of those good-news/bad-news situations. N-myrist… Read More
The number of stories and journal articles about how CRISPR DNA-editing technology works, has worked, and is planned to work are beyond counting. How about an article about how to stop it in its tracks? That’s this one, just published in Cell from a multicenter team in Cambridge and New York. It describes a screening… Read More
This is a good brief overview of a topic that’s becoming more important all the time: analysis on the single-cell level. And as the authors mention, it’s partly a case of wanting to do this, and partly a case of there being no other choice. Larger pooled tissue samples just don’t have the level of… Read More
Here’s some medicinal chemistry combined with synthetic biology for you. Many people are used to thinking in terms of finding small-molecule probes for various cell targets, and those are valuable things. But what if you want to control a certain population of (for example) ion channels, but there aren’t any compounds that will do the… Read More
