molecules of the month

“compound 37” is an inhibitor of the ATG7 E1 ligase through an interesting substrate-assisted covalent mechanism. Rather than covalently modify ATG7 directly, the molecule reacts with the E1 ligase substrate, Ubl, to form a Ubl-inhibitor adduct which non-covalently inhibits ATG7. This mechanism has been employed by Takeda successfully in the past against a number of other related targets such as NEDD8-activating enzyme. Compound 37 is one of three molecules from this article demonstrating in vivo inhibition of the autophagy process.