How do you sort out a P450 inhibition problem?
I had honestly forgotten about contributing to a book chapter, when the email came through that it was finally published. “Strategies to Mitigate CYP450 Inhibition” was co-written with Marcel de Groot and Sarah Skerratt several months ago. Of course, it went through editing and joining to the rest of the book chapters, and I guess ‘lockdowns’ may or may not have helped, hence, this is why I ended up forgetting about it. We wanted to write a chapter that was not a long compendium of med chem examples, but rather a strategy, where at its heart, was a flow chart of ‘what to do’ if P450 inhibition was found with a series. This includes testing and re-testing, and look for assay interference, before looking for medicinal chemistry solutions. We then included analysis on large datasets of results and Matched Molecular Pair Analysis to show robust methods to reduce binding for each of the major give isoforms. Overall, we hope you find this useful!
Strategies to Mitigate CYP450 Inhibition
From the book:
The Medicinal Chemist’s Guide to Solving ADMET Challenges
Alexander G. Dossetter, Marcel J. de Groot and Sarah E. Skerratt
https://pubs.rsc.org/en/content/chapter/bk9781788012270-00220/978-1-78801-227-0