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.
Drug discovery folks spend a good amount of time and effort dealing with cell membranes. Our drug candidates stick to them, get imbedded in them, might have to slip through them to get to their target proteins, or may target proteins that are localized in them, can get actively transported through them or actively pumped… Read More
Antibiotic discovery is always welcome. Here’s a new one from a well-searched area (Actinomycetes extracts), and the authors (university teams from McMaster, Indiana, and Montreal) did a lot of groundwork to make sure that they weren’t just going to rediscover known agents. That’s a serious problem with broad-based antibiotic scre… Read More
The open-source program that I use for literature management (Zotero) set off a feature not long ago that I didn’t realize it had. A red banner appeared across the top with a notice that a paper that I had in one of my collections had been retracted. That’s pretty handy: a red X now appears… Read More
Figuring out an unusual natural product’s activity can be a difficult but rewarding exercise. Deep evolutionary time has provided us with a bizarre range of chemical structures that are presumably not being synthesized by organisms for the sheer fun of it – these things are acting as signaling molecules, antifeedants, poisons for the co… Read More
Back for more, and welcome to 2020! Frankly, that sounds like a year out of a science fiction story, but I will admit that it’s not the first year about which I’ve had that thought, either. Let’s get right into the drug discovery with a new paper from a team at UNC in the very fashionable… 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
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
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
