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 my experience, most organic and medicinal chemists are always ready to hear about the latest results in two branches of the science: things that explode and things with weird smells. Maybe we are in our way “singularly in touch with the primitive promptings of humanity”, as Captain Grimes says in Decline and Fall (although… Read More
Figuring out an unusual natural product’s activity can be a difficult but rewarding exercise. Deep evolutionary time has provided us with a bizarre range of chemical structures that are presumably not being synthesized by organisms for the sheer fun of it – these things are acting as signaling molecules, antifeedants, poisons for the co… Read More
Like many organic chemists, I find natural products very interesting, since their structures are often things that I would never imagine making (and in some cases have trouble imagining how to make at all!) But there’s a feature of the literature in that area that not everyone appreciates: the fact that a reasonable number of… Read More
Here’s a thorough review of a topic that combines complex drug development issues with complex chemistry: trying to optimize the structures of natural products so that they can be more effective drugs. There are detailed looks at examples like the tetracyclines, the polyene macrolides, pactamycin, geldanamycin, and the thiostrepton-like pepti… Read More
In a perverse way, I’m enjoying how modern organic synthesis is upsetting the classic undergraduate sort of test-question syntheses. You know – Grignards, ester condensations, oxidation and reduction of carbonyls, Wittigs, Sandmeyer reactions, Friedel-Crafts, good ol’ hammer-and-tongs bond formation. I had sophomore organic back i… Read More
The proteasome is quite the structure. It is the shredding unit of the cell, where no-longer-needed proteins go to be ripped down to their components for recycling, and it’s become a more and more important part of drug discovery over the years. For one thing, all this fashionable targeted protein degradation work is about sending… Read More
Microbiome, microbiome – you haven’t been able to turn around in this business the last few years without hitting some sort of story about the microbiome. It’s easy to roll your eyes and decide that it’s all hype, but that’s the thing: it really is important. It can’t be dismissed just because we don’t unde… Read More
Here’s an unusual twist for you. Many readers will be familiar – to their regret, most likely – with the story of T*ring Pharmaceuticals (name redacted slightly in order to not defame a great scientist whose name was tacked on to this outfit for no reason other than advertising). Their first idea was to go… Read More
Some readers may recall this post from 2015, which details problems with a natural product isolation paper in PLOS ONE. The compound, named Xinghaiamine A by the authors, was. . .well, let’s say extremely unlikely, and I think anyone who looks at the structure in that earlier post will agree. And that spans several levels… Read More
This paper (from two groups at Yale’s chemistry department) addresses several important things that fall into the “important irritants” category in synthesis and molecular biology – or maybe that should be “irritatingly important”. We spend a lot of time thinking about proteins in terms of their primary sequence… Read More
