- Here’s a very interesting rundown on an issue that became apparent during the coronavirus vaccine development period. You may remember (if you haven’t expunged that entire period from your mind!) that although the mRNA vaccines were the biggest successes, that adenovirus-vectored vaccines from AstraZeneca and Janssen/J&J were also in the race. But those ran into trouble as they were rolled out into larger populations (I wrote about this here at the time). All drugs (and that includes all vaccines) are […]
- After having just written last week about the FDA’s refusal to consider Moderna’s mRNA vaccine application, the agency has apparently reversed course and told the company that they will accept it. According to Stat, the agency will review the vaccine in 50-64-year-olds via the regular pathway and over-65s via accelerated approval with a required post-marketing study if approved, and has set a deadline of August 5. This is good news right on the face of it, and you have to […]
- This weekend brought news that the Russian opposition leader Alexei Navalny was poisoned in prison by the compound epibatidine. That is not (to put it delicately) the first thing one would have expected, so I wanted to give a little background on this compound first. It’s a toxin isolated from a frog species found in Ecuador and Peru (and a few of its relatives), and like all poison frogs it is a very festive-looking creature indeed. That is of course […]
- Edit: as of February 19, this paper has picked up (rather rapidly) an Editorial Expression of Concern. ". . .concerns have been raised regarding inconsistencies between the registration record of this trial on clinicaltrials.gov and (the) published version (of) the study protocol, as well as with some of the findings in this study" That doesn't sound good so far. The editors say that they are investigating and will report with more details, and I'll add those here as they appear. […]
- I’ve written before a time or two about retroviral DNA, which is something that we’re all carrying around whether we feel like it or not. Over evolutionary time there have been a number of events where human germ cell lines have had these sequences inserted into them by retroviral infection, and we’ve been living with them ever since. Mutations occur, of course, and some of these sequences are rather decayed by now, but it seems that between 5 and 10% […]
- Last night brought news that the FDA has refused to review Moderna’s application for their new mRNA influenza vaccine, and more details have emerged so far today. All of them are infuriating. Right off, let’s just make clear that an outright refusal-to-review rejection like this is quite unusual, since biopharma companies (large and small) typically work with the FDA during their trials to make sure that things are being run in a way that the agency finds acceptable. Why wouldn’t […]
- The list of weird ideas for using bifunctional molecules is nowhere near reaching its end, and this paper is another example of that. There have been scattered reports over the years of small molecules that inactivate particular proteins by causing them to assemble into inappropriate multimeric forms, which are inactive in themselves and/or degraded by cells once formed. The authors here are deliberately aiming at that effect. To do that they target proteins that are known to self-assemble into homodimers […]
- This is a pretty weird idea, but it seems to work. I’ve written many times about aspect of crystallography, but there’s one great big overarching concern in that field that you have to get past: can you even get crystals of your desired compound at all? Advances in x-ray crystallography and electron diffraction have helped to push the size and availability of useful crystals further and further, and we can now get experimental structures from samples that once would have […]
- Here, thanks to Milkshake over at Org Prep Daily, is an example of what the scientific literature is slowly turning into under the onslaught of chatbots. The Royal Society of Chemistry journal Sustainable Energy and Fuels has a paper in it that's been up for a while (published in August of 2024) with the unremarkable title of "Critical insights into eutectic molten hydroxide electrolysis for sustainable green hydrogen production". It's not a topic that I pay that much attention to, […]
- Here’s one that I hadn’t heard of: there is epidemiological evidence that a medical history of cancer seems to decrease the risk of an Alzheimer’s diagnosis. From the looks of it, this observation has survived several attempts to make it go away. That’s exactly how you should treat such an interesting hypothesis, because it gets much more interesting if you can’t easily dismiss it. Very roughly, a cancer diagnosis appears to lower the risk of later Alzheimer’s disease by around […]
- This is a brief but informative article at Nature Reviews Drug Discovery from folks at Boston Consulting Group looking at the 2025 drug approvals at the FDA. There were 54 such (excluding diagnostic imaging agents), which is consistent with the landscape since 2014 (the average since then has been exactly that!) 2005-2013 average, by contrast, was 30 new drug approvals. In fact, in that post 2014-period, there’s only been one year (2016, with 28 approvals) that wasn’t higher than any […]
- This new paper is worth examining as the probable state of the art in LLM-based chemical reaction handling and prediction. The authors report a system (MOSAIC, Multiple Optimized Systems for AI-assisted Chemical prediction) that takes a graphical representation of a proposed new reaction and attempts to produce a written synthetic procedure to realize it in a lab. This is done by creating a fingerprint profile of the proposed reaction using RDKit and Morgan representations of the starting materials and the […]
- Not many people outside of infectious disease specialists may realize it, but the order Mononegavirales is really bad news for human health. Inside that one you can find measles (the fashionable infection of 2026, damn it all), RSV (always with us), mumps, rabies, and even Ebola, which I very much hope does not become a hot item in any year. There are plenty of differences between all these (there are eleven families in this order), but something that the Mononegavirales […]
- Here’s a paper that illustrates an important topic in med-chem, one that an awful lot of ink and pixels have been spilled on over the years. When we talk about affinity of a drug to a target, the binding constants that we measure have a lot of thermodynamics packed inside them. Like every other chemical reaction and interaction, the favorable ones show a decrease in overall Gibbs free energy for the system (delta-G), but one should never forget that the […]
- Let’s take a look at the vaccine situation here in the US, because it’s (1) important and (2) not very pretty. A lot of it can be summed up in the recent statements by the head of the Advisory Committee on Immunization Practices (ACIP) at the CDC, Dr. Kirk Milhoan. This is of course the committee that last year saw its entire roster fired by Robert F. Kennedy Jr. and replaced by what I will politely refer to as a […]
- This is one of those papers that really makes you wonder what you’re missing when you look around you. The authors are looking at what might sound like a rather uninteresting question – what happens when you dissolve alkylamines in water? I would have said (and I’ll bet that many of you would have too) that well, you get a solution of alkylamine molecules in water. I mean, there will be solvation shells and there will be hydrogen bonding around […]
- I’ve written a number of times over the years here about the placebo effect, and needless to note there’s still a lot more to be said. This new paper is stark evidence of that! It notes that there is evidence that (at least in mice) that the dopaminergic mesolimbic pathway is known to help modulate immune function, but is also involved in expectations of positive outcomes. This raises the possibility of a direct neural/biochemical linkage that might be behind some […]
- I think that this article is a useful one for medicinal chemists to read, because it gets at a lot of the “received wisdom” about what sorts of compounds are good development candidates. On the most basic level, there’s not much disagreement: you would like an orally delivered agent with excellent potency and selectivity, given at a relatively low dose with good bioavailability and once a day, that has normal-looking pharmacokinetics to give you blood levels that cover the target […]
- Ah, G-protein coupled receptors. They’re an absolute mainstay of drug discovery and have been for many decades, and one of the first projects I worked in when I joined the industry was an effort to produce selective muscarinic M2 antagonists. A few years back I had the chance to meet Bob Lefkowitz (Nobel for GPCRs, along with Brian Kobilka), and I mentioned to him that back in the early 1990s when I was working on them I thought I understood […]
- I haven’t blogged on the microplastics-in-human-tissue reports, but they have certainly been disturbing. Over the last few years, there have been studies suggesting that such species have been accumulating in human brain tissue, the cardiovascular system, testicular tissue and more. There are obviously a lot of microplastic particles out there, considering the environmental wear on so many years of plastic packinging, etc., and it seems unlikely that they’re improving anything. But I will admit to being surprised at the idea […]
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