ML323 (ML 323) is a potent, selective, reversible inhibitor of the USP1/UAF1 deubiquitinase complex with IC50 of 76 nM.
ML323 displays >1,500-fold selectivity versus USP2, USP5, USP7, USP8, and USP46/UAF1.
ML323 potentiates the cytotoxicity of cisplatin and increases endogenous monoubiquitination levels of both PCNA and FANCD2, two known cellular targets of USP1/UAF1.
ML323 possesses a promising in vitro ADME profile.
