molecules of the month

The BMS IDO1 inhibitor, BMS-986242, is a clinical candidate in a Ph. I/II study in combination with nivolumab for cancer. Like me, you probably had to look twice at this molecule since it’s so similar to linrodostat, which we covered recently. Forming the reverse amide of linrodostat appears to improve the PK profile and also removes a potential reactive aniline metabolite. Making the reverse amide of an amide starting point is a med. chem. tactic that’s often suggested, but it’s rare to see it play out so well, especially when both the amide H-bond donor and acceptor making interactions with the target.