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.
Here’s a solid med-chem paper from Merck on the topic of extending half-life for small-molecule drugs. This obviously is most important (and can have the biggest effect) if your compound has a short half-life after dosing to begin with (and plenty of compounds do). As the paper notes, if you have constant clearance for the… Read More
Never give up on drug delivery ideas – that’s one of the big points I get out of this paper. The authors, part of a multi-center team from sites in Italy and Germany, have previously shown that calcium phosphate nanoparticles could be a good carrier for delicate cargo such as microRNAs. Such things tend to… Read More
Here’s a good short review on a subject that doesn’t come up too often in drug discovery, but can be a major headache when it does: atropisomerism. There are all sorts of structural isomers possible for organic compounds, and students in their second-year class have a joyful time learning them and keeping them straight. But… Read More
If you’re looking for a good example of evolution-as-a-tinkerer, the melanocortin receptors would be a good place to start. From a single starting point, they’ve ended up as a family of related proteins that do completely different things. And the hormones that bind to them have radiated out as well: they’re all derived by process… Read More
The cell membrane – the fundamental architecture of living things, the foundation of how our very bodies are organized – is a major pain in the behind. I express this ungrateful opinion merely because over the years it has rejected entry to some of my best ideas for drug candidates, and I bear a grudge. Read More
We medicinal chemists are used to thinking about small molecule drugs – it’s what we do. And we’re also comfortable with having a category in our worldview that we assign to “biologics” – proteins, mostly, many of them antibodies, which can also be extremely therapeutically effective under the right conditions. B… Read More
I like this review, but I’ve seen it before. Well, not this exact manuscript, but every few years it seems there’s another one with a similar title, something about “Incorporating Silicon Into Drug Structures”. I am guilty of the exact same thing, though: here’s a blog post from 2004 on the topic, and here’s one… Read More
This is a neat article at Bloomberg about the production of botulinum toxin (BTX, aka Botox). This is a drug that has some rather special handling involved: A baby-aspirin-size amount of powdered toxin is enough to make the global supply of Botox for a year. That little bit is derived from a larger primary source… Read More
Drug delivery – now that’s a tricky field. The variety of drug substances is large, and the ways that they’re taken up and distributed in living systems are many. And we’d like control over the process, which we don’t often have. A typical kid’s question is “How does the aspirin know where the headache is?… Read More
EGFR is a growth-factor receptor protein that’s well known as a cancer target, and there are a number of drugs that target its kinase activity in order to shut it down. But as is also well known, many cancer cells are rather genomically unstable, and throw off mutations constantly. One of the most common problems… Read More
