- I recommend anyone who wants to learn more about generic drug manufacturing to read this article at the New York Times (it’s a gift link, free to read). There’s been a lot of coverage of drug manufacturers “on-shoring” production and packaging in response to pressure from the Trump administration, and there is definitely some of that happening (although it doesn’t happen as quickly as it might seem to). But this is another world entirely. That’s because the generic drug business […]
- I have lost count of the number of times over the years that I’ve said “Huh, I didn’t think mass spec could do that”. So you’d think that I would be used to this by now, but apparently not, because that was my exact reaction to this new paper. It’s from a team of groups at Leiden, Utrecht, and Jena, and they report a “self-encoded library” technique for some pretty large-scale screening. It should be noted up front that there […]
- It is a longstanding dream of mine that some day, some year I will no longer feel obliged to write disparaging blog posts about Sarepta and their Duchenne muscular dystrophy drug portfolio. I have been doing that for a loooooong time now (twelve years?) as the company, with what from one perspective is admirable persistence, has continued to develop and test various small-molecule drugs and gene therapies. My misgivings have come from the clinical trials of these agents, which have […]
- I’d like to take a bit of time to note this paper and its authors. It was published in May of this year in JACS, and it was about the conversion of carbon dioxide to methane. That’s certainly of great interest – it’s basically “reverse combustion”, and as you can imagine there are a lot of people interested in taking industrial carbon dioxide emissions and sending them back around by such a process. You could even imagine a technology that […]
- The “nocebo” effect is something that makes a lot of sense when you think about it, but it still seems weird. Everyone has heard of the placebo effect, where some interventions tend to have a beneficial effect if you think that they’re having (or going to have) a beneficial effect. There is no doubt that this is real, although its magnitude varies a great deal depending on circumstances, as it well should. The nocebo effect is just that with the […]
- Here’s another example of an idea that has been kicking around for years in medicinal chemistry without ever really breaking through: substituting a silicon atom for a carbon. To be fair, most of the time this doesn’t seem to do all that much, while introducing various uncertainties around ADME and toxicity (since we don’t have all that much experience with organosilanes as drugs). So you can see why we’re not overrun with “silyl switch” compounds. But at the same time, […]
- I think that I can guarantee that you haven’t heard this phrase before: “ballistic microscopy”, the subject of this recent preprint. What the authors describe a combination of near-medieval technology on the one hand and cutting-edge analytical work on the other. They are bombarding cells with focused streams of gold nanoparticles (which range from 50 to 1000 nm diameter). These things are traveling at speeds up to 1 km/sec (over 2000 miles per hour (edit: fixed!)) and blast straight through […]
- This is a rather unexpected article that suggests that some mRNA vaccines can potentiate the actions of some immune-checkpoint therapies used in oncology. Specifically, the authors find that the mRNA coronavirus vaccines significantly increased overall survival rates in those patients who were getting anti-PD-1 antibodies as immune checkpoint inhibitor therapy (!) In a welcome reverse of the usual way we end up studying cancer therapies, this effect could be replicated in mice. There was a strong synergistic effect of mRNA […]
- Ah, quantum mechanics. We’ve known about it for a hundred years now, and it’s still as weird as it ever was. This paper has a case in point: the authors are investigated a catalytic hydrogenation reaction, the reduction of a benzyldehyde to a benzyl alcohol with hydrogen gas and a palladium catalyst dispersed on a titanium particle surface. There are a lot of ways to get this sort of reaction accomplished, and they occur through a lot of different mechanisms. […]
- Now, transcription and translation are indeed wonders of nature. The constant reading-off of our genetic code and its expression into proteins kind of has to be at that level, you’d figure, for living cells to work at all. But it’s important to remember that not-so-exact versions of these things are important, too. I’ve written about how error-prone mechanisms can be useful for bacteria and viruses (and indeed, how switching gears to these can be an outright roll-the-dice survival mechanism). But […]
- As I have stated several times over the years here, intrinsically disordered proteins make me uncomfortable. I mean intellectually; biochemically they are keeping me (and the rest of us) alive, because they are crucial to cellular function in a number of ways. My mental difficulties are because of my background as a small-molecule organic chemist, because small molecules – okay, most small molecules – have defined structures and shapes. That leads right to a mental model of enzyme function where […]
- Never, ever assume that you know everything that a given drug molecule is doing inside the body – where it’s going, what it’s binding to, any of those things. That’s a lesson that gets illustrated over and over, and this recent paper is yet another example. It’s about rapamycin, which is used after transplants to modulate immune rejection, as a coating in vascular stents to try to prevent the blood vessel closing up again (restenosis), and for some skin disorders, […]
- This is a worthwhile new paper on the use of a general Large Language Model (LLM) for generating chemical analog ideas, and it’s definitely one of the most believable of its kind that I’ve seen. Readers will know that I have developed a reputation as an AI skeptic, but I prefer to think of myself as an “AI realist”. And there are thus aspects of this paper that I can see working out in a useful way. The authors are […]
- There are people (and companies) out there who feel that the immuno-oncology boom has run its course and that there are far fewer good opportunities out there than there were a few years ago. Well, I’m not putting my own money on the line, so perhaps that gives me a different perspective, but I don’t quite get the lack of enthusiasm. Oncology is hard, immunology is hard, so the combination of the two is going to be. . .guess what. […]
- This morning’s Nobel Prize in Chemistry is one that’s been anticipated for several years now: it goes to Susumu Kitagawa of Kyoto, Richard Robson of Melbourne, and Omar Yaghi of Berkeley for metal-organic frameworks. So what’s a MOF? This goes back to the idea of “coordination chemistry”, a huge topic in the inorganic and metal-organic fields. That’s the ability of metal ions (pretty much all of them, across different elements and in different oxidation states) to interact with organic chemistry […]
- There’s a lot of interest – heck there has always been a lot of interest – in getting results from assays that more closely match what you get from living creatures. And it’s not easy. A prime example has been liver function (and its evil flip side, liver tox). You can biopsy animal livers (and even human ones, ouch) all you want and get piles of hepatocytes fresh from the source. But when you culture them in vitro, they rapidly […]
- It’s Nobel Week again, and we lead off 2025 with the prize in Medicine/Physiology going to Mary Brunkow (at the Institute for Systems Biology), Fred Ramsdell (at Sonoma Biotherapeutics) and Shimon Sakaguchi (Osaka Univ.) They’re being recognized for their work in the late 1990s and early 2000s that led to the realization that there were such things as regulatory T cells, which are now often referred to by aficionados as “T-regs”. So what are these cells, and why is their […]
- I’ve been traveling, so I want to take the opportunity to catch up with all the acetaminophen/paracetamol/Tylenol stuff the Trump administration has been connecting to autism. As everyone will have heard, HHS and the White House are claiming that exposure to the drug during pregnancy is a cause for the rising incidence of autism diagnoses over the last few decades. Let’s dispose of that one right here in the first paragraph: there is no good evidence supporting such a causal […]
- I'll be taking a brief break here – there might be a new post late next week, but we'll see! If not, then look for things to resume on Monday the 6th. Nothing bad, nothing big, just a lot going on at once. I'll see everyone shortly!
- This is a sort of paper that you don’t see too much if you most read chemistry and biology journals. It’s not presenting lab results in either of those fields per se, but asking what it means to be a chemist at all. It’s quite interesting, but I do have to raise an immediate point before discussing the rest of the work: it’s based on an in-depth survey of ideas and attitudes among chemists in both academia and industry, early- […]
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