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.
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
I wrote here about a paper from Cold Spring Harbor labs that invalidated MELK as a cancer target. That was straightforward enough: knocking it out via CRISPR across a whole range of cancer cell lines had no effect on their growth at all, so it’s kind of hard to make the case that it’s an… Read More
Here’s a topic that came up in my Twitter feed the other day – I fear it’s unanswerable, but I’d like to hear what people have to say about it. Drug discovery projects start, of course, from a selection of possible chemical matter and chemical series, and they eventually narrow down to a clinical candidate. Read More
Here is an interesting paper in Nature Biotechnology on computational drug design, and if you read it without reading any of the accompanying articles about it, you will have a perfectly good time. There are things that you will be impressed by, and there are things that you will argue with, but that’s how most papers… Read More
The Nrf2 pathway has been a hot area of research for some years now, particularly in oncology. It’s a basic-leucine-zipper transcription factor that under normal conditions stays mostly out in the cytosol, where it’s under tight regulatory control. Under cellular stress, though, it heads into the nucleus and fulfills its transcription-f… Read More
This is a good review from AstraZeneca scientists on phenotypic screening in neurodegenerative disease (by which one means Parkinson’s, Huntington’s, frontotemporal dementia, Lewy body dementia, and of course Alzheimer’s). And it’ll serve as a good intro to the challenges in these two fields in general, and to why they inter… Read More
I’ve written several times here about phase-separated condensates in cells, but now comes a rarity: a paper with some evidence for a therapeutic application. Everyone in the field has been thinking along such lines, naturally, but this is the first small-molecule screen that I’ve seen that tries to tie modifying condensate behavior in t… Read More
Here’s a new look at the various ways that small molecules can affect a well-known drug target (the estrogen receptor) and it shows us that we’re all going to have to look at these things more carefully than we do. Now, to be fair, the ER is already fairly complicated, because it’s a nuclear receptor. Read More
This is a pretty interesting paper on several levels. It sheds light on Mucin I kidney disease (MKD), on protein degradation pathways (a hot topic these days, as those in the industry well know), and it also provides a small molecule lead compound. It’s a large multicenter team, starting off with the Broad Institute, but… Read More
Here’s an interesting new paper from Lilly (brought to my attention by Ash Jogalekar on Twitter). “Creating a virtual assistant for medicinal chemistry” is the title, but fear not: this is not something that’s come to elbow you aside at the bench. Well, not yet. What they’re talking about is a software agent that is… Read More
