Unusual Toxicity With a Protein Degrader Molecule (opens in new tab)

Those of you who lived through the worst of the “Rule of Five” era in medicinal chemistry will well appreciate that we are working with a lot of compounds now that cheerfully violate some of those strictures. Molecular weight might be the first on the list, thanks to the number of large bifunctional molecules (for targeted protein degradation and other ideas) that have been in development. In retrospect, there were people (and departments, and whole companies) that put blinders on themselves ...