ML-792

ML-792 is an inhibitor of SUMO-activating enzyme (SAE; IC₅₀s = 0.003 and 0.011 ?M with small ubiquitin-related modifier 1 (SUMO-1) or SUMO-2, respectively, as the ubiquitin-like proteins).¹ It is selective for SAE over NEDD8-activating enzyme (NAE) and ubiquitin-activating enzyme (UAE; IC₅₀s = 32 and >100 ?M, respectively). ML-792 inhibits SAE activity and decreases global SUMOylation in HCT116 human colon cancer cells (EC₅₀ = 0.019 ?M), as well as decreases the viability of MDA-MB-468 human breast and A375 human melanoma cells (EC₅₀s = 0.06 and 0.45 ?M, respectively). It also induces mitotic defects in HCT116 cells and impairs chromosomal segregation in HCT116, A375, and COLO 205 cells. ML-792 reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 150 and 200 mg/kg twice per day.²

1.He, X., Riceberg, J., Soucy, T., et al.Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitorNat. Chem. Biol.13(11)1164-1171(2017) 2.Langston, S.P., Grossman, S., England, D., et al.Discovery of TAK-981, a first-in-class inhibitor of SUMO-activating enzyme for the treatment of cancerJ. Med. Chem.64(5)2501-2520(2021)