ML-364 is a reversible inhibitor of ubiquitin-specific protease 2 (USP2), a deubiquitinase, that has an IC50 value of 1.1 ?M in a fluorescence-based assay using di-ubiquitin substrates.1 It inhibits USP8, which is closely related to USP2, with an IC50 value of 0.95 ?M in the same assay. It has no activity at the proteases caspase-6, caspase-7, MMP-1, MMP-9, and USP15 or at 102 kinases in a panel including cell cycle regulators. ML-364 increases cyclin D1 degradation (IC50 = 0.97 ?M) in HCT116 colorectal carcinoma cells. It induces arrest of the cell cycle at the G1 phase in Mino mantle cell lymphoma and HCT116 cells and inhibits proliferation of HCT116 cells (IC50 = 3.6 ?M). It also decreases homologous recombination-mediated DNA repair in DR-GFP U2OS cells.
1.Davis, M.I., Pragani, R., Fox, J.T., et al.Small molecule inhibition of the ubiquitin-specific protease USP2 accelerates cyclin D1 degradation and leads to cell cycle arrest in colorectal cancer and mantle cell lymphoma modelsJ. Biol. Chem.291(47)24628-24640(2016)