ML-792

ML-792 is a potent and highly selective small molecule inhibitor of the SUMO-activating enzyme (SAE), which is involved in the post-translational modification process known as SUMOylation. ML-792 inhibits SAE activity at nanomolar concentrations (IC50 ≈ 3 nM for SUMO1, 11 nM for SUMO2) with strong selectivity over related enzymes, such as the NEDD8-activating enzyme[3][7]. ML-792 leads to a rapid and near-complete loss of cellular SUMOylated proteins, inducing cell cycle arrest, endoreduplication, and apoptosis in cancer cell lines, especially those with MYC amplification. It has shown efficacy in preclinical models, such as reducing tumor growth in mouse xenograft models[9], and offers therapeutic potential particularly in Epstein-Barr virus (EBV)-associated malignancies and potentially other cancers reliant on SUMOylation, such as pancreatic cancer and prostate cancer[1][2][4][5]. ML-792 does not cross-react with the NEDDylation or ubiquitinylation machineries and thus provides specific molecular insight and potential clinical utility as an anti-neoplastic and anti-viral agent[2][5]. ML-792 was initially developed by Millennium Pharmaceuticals and served as a chemical precursor to clinical-stage SAE inhibitors such as TAK-981[2][8][10].

Other names

1644342-14-2