- Sorry to have been out of touch for the last couple of days, but I'm currently fighting off what appears to be some annoying virus. Mild upper respiratory symptoms, recurrent fever, body aches – the whole package. Interestingly, antibody tests show negative for both Covid and influenza A and B. So I don't know quite what I'm dealing with there, but the default flulike treatment regimen is in effect: as much sleep as feasible, lots of liquids, light on the […]
- Many people have asked me about my opinion on this recent Alzheimer’s paper, and my opinion lands in the large zone of “interesting work that I hope is followed up on”. That may come as a disappointment, because some of the headlines about this paper have been breathless Cure-For-Alzheimer’s stuff, which is always a danger in this area, and for all I know there may be some folks out there who’d like to see me dismiss these results as yet […]
- Happy New Year! Science blogging resumes on Monday. But I have to get this off my chest first: Let me start off this first post of 2026 by acknowledging that 2025 was, in many ways, a horrible year. I say that particularly by the subject matters of this site – biomedical research and science in general. The Trump administration moved quickly last year to attack federal research funding from every single angle they could think of, and went on to […]
- Actual scientific work is definitely slowing down around here as the holidays approach. As I often do, I wanted to (re)post some recipes of foods that go well with the season (or perhaps with cold weather in general). I've rounded up a few new photos of the results as well! All of these are synthesized regularly here at Pipeline HQ, and I can personally vouch for all of them after long experience. If you'd like to see the whole range […]
- One of the constant themes of cell biology, chemical biology, and drug discovery is trying to find out where things are in cells. It isn’t easy! You can’t just pick out a small molecule, a protein, a lipid, a polysaccharide or what have you and chase it around a living cell with some sort of microscope, because there’s generally either no good way to detect such things specifically or certainly no way to do it on the small scale required. […]
- I’ve kicked around the idea of doing some “Where Are They Now” posts here, and I think that this is as good an occasion as any. Back in 2018, I wrote about a new company called Verge Genomics that was using AI/ML methods to go after neuroscience targets like ALS, and my eye was caught by statements like “Instead of tediously screening millions of drugs, the algorithm will computationally predict drugs that work” and “We've discovered a way to map […]
- Here’s a neat look at microbial natural products from a chemical diversity standpoint. Of course, natural products have a fearsome (and well-earned) reputation for displaying structures that we humans would never have gotten around to making – or even thinking of – but once you get that internalized, there are some interesting patterns and lessons. The author (Roger Linington at Simon Fraser Univ.) is also looking at two trends that at first seem to be at odds with each other: […]
- We have been making small-molecule inhibitors of kinase enzymes for quite a while now in medicinal chemistry, and I would not even want to guess how many such compounds have been described in the literature. As an aside, this is usually the point where someone who’s been around as long as I have recalls that there was a time when people thought – not without some reason – that making such selective kinase inhibitors might not be possible at all. […]
- It’s been obvious for many years now that growing antibiotic resistance is a problem, and that it could turn into a very bad one. There has been a great deal of work put into trying to understand the nature of these resistance pathways, but if you’re studying bacterial pathogens in the modern world, you’re showing up at the crime scene long after the break-in. You might be surprised to learn (I was!) that there is actually a resource of pathogenic […]
- I found this to be an interesting paper, and it uses an idea that’s not always easy to realize. There are a lot of time when we’d like to be able to use small proteins and peptides as drugs, but they often have poor pharmacokinetics (absorption, membrane penetration, and most especially metabolic liability). In addition, some of these small-protein ideas can end up being immunogenic, since your body can react to them like the foreign substances they are, with your […]
- I enjoyed reading this new synthetic paper, because I can still remember when I learned about the good ol’ Sandmeyer reaction in sophomore organic chemistry class and these authors are among the many people trying to replace it. There’s a reason for that, because while the Sandmeyer is definitely old, it ain’t always good. It’s a reaction that lets you take an aromatic amine (of which there are a great many) and convert that amino group into a wide variety […]
- The whole “Are there weird electric fields at the surface of water droplets” question is not getting any easier to understand. I last wrote about this topic here). There are several subsidiary questions that go off in different directions: does unusual chemistry actually happen at air-water interfaces (and is this more prominent, as you might expect if true, in small droplets that are mostly surface area?) Or are these reports (mostly) experimental artifacts? If it does happen, what’s the mechanism? […]
- Some chemistry today, drawn from real life (mine, anyway). I was setting up a short series of palladium-catalyzed couplings the other day (Buchwald-Hartwig type, C-N bond formation), and since there were very close precedents to my structures in the chemical literature, I naturally just borrowed the known conditions. There was nothing out of the ordinary about them; it seemed as if they’d work about as well on my starting aryl bromides as it did on the ones already described. (Edit: […]
- Well, here’s another report of a GLP-1 agent being tried in Alzheimer’s patients (after this recent post was written). The last one didn’t show much, so let’s have a look. In this trial, 204 patients with mild-to-moderate Alzheimer’s were treated with liraglutide (daily injection) versus placebo for one year. The doses started at 0.6mg and worked up to 1.8mg, which is the typical starting dose for diabetes therapy working up to the maximum approved one. The primary outcome was looking […]
- It is next to impossible to keep up with all the chaos in the Trump administration’s staffing of the public health agencies (NIH, FDA, and all the ones under them). I haven’t tried to cover it all blow-by-blow, because it would exhaust me and exhaust you the readers, and to what end? You can make out the main points of the Trump/RFK Jr. approach pretty easily. One of those is clearly, obviously, a multipronged attack on the practice of vaccination. […]
- This is a good look at the current state of the art in creating peptidic binding ligands to protein targets out of thin air – well, “one-shot computation” is probably the more preferred term, but you get the idea. One expects this to start to be more feasible with such peptide ligands because of several factors: the modular nature of the peptides, for starters, combined with a limited number of amino acid building blocks both make the problem more bounded […]
- There have been some interesting failures recently in Alzheimer’s trials. As long-time readers will know, I consider basically all Alzheimer’s drug trials to have failed to one degree or another, and particularly when it comes to clearing the “will improve patient’s lives in the real world without putting them at too much risk” hurdle. But these two are notable because they’re aimed outside the usual amyloid zone. First off, Novo Nordisk reported that semaglutide (the company’s GLP-1 agonist drug, of […]
- This paper advances a metabolic hypothesis that I certainly didn’t see coming. One of the great mysteries about alcoholism/alcohol use disorder is its underlying biochemical drivers. There’s obviously a behavioral and psychological component, but there are physical and metabolic ones too, and trying to untangle those has been an effort of many decades. The authors here note a long-running series of observations about alcohol and sugar consumption. For one thing, laboratory rats that are given access to alcohol will in […]
- Here’s a phenomenon – yet another one – that never crossed my mind before. It’s long been known that enzymes that catalyze proteolysis (cleavage of peptide bonds) can, under certain circumstances, catalyze the reverse reaction of peptide bond formation. Folks who have had to think about chemical kinetics will immediately realize that those conditions would include high concentrations of the two cleavage products and low concentrations of the longer protein substrate, an example of Le Chatlier’s principle in action. It’s […]
- This is a very useful article on phenotypic screening, and is well worth a read. And if you haven’t done this sort of screen before but are looking to try it out, I’d say it’s essential. The authors (both with extensive industrial experience) go into detail on the factors that can make for successful screens, and the ones that can send you off into the weeds. There are quite a few of the latter! For small molecule screens, you need […]
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