molecules of the month

Context. “Compound 24” (Amgen) is a kinesin-like protein 18A (KIF18A) inhibitor being developed for a subset of cancers with chromosomally unstable tumor cells. Their first-in-class, oral clinical candidate, AMG 650, was recently disclosed at ACS Spring 2022 and is in Ph. I for cancer. Both antimitotic drugs targeting microtubules and those targeting essential mitotic kinases have been studied extensively, although the high toxicities associated with these agents and associated moderate efficacy have dampened interests in them over the years. Common events associated with MT inhibitors are dose-limiting neurotoxicities, myelosuppressive, and gastrointestinal effects (almost all approved MT inhibitors have caused one or more of these side-effects in at least 50% of treated patients). These limitations spurred researchers to search for alternative…