ML-792 is a specific inhibitor of small ubiquitin-like modifier (SUMO) activating enzyme (SAE), which can inhibit SAE/SUMO1 and SAE/SUMO2 with IC50 of 3nM and 11nM, respectively[1]. The SUMO protein pathway can control a series of important biological processes, including cell death, proliferation, differentiation, metabolism and signal transduction, by diversifying the functions, half-lives and partnerships of in situ target proteins[2]. ML-792 is often used to study the role of SUMOylation in cancer, neurodegenerative diseases and viral infection[3, 4].
In vitro, ML-792 (0, 1, 5μM) treatment of 5-FU-resistant cell lines (HCT-8/5-FU cells) for 12-16 days significantly reduced the number of cell colony formation and reversed the cell's 5-FU resistance[5].
In vivo, ML-792 (50, 100mg/kg) was intraperitoneally injected into mice bearing HOS cell xenografts, which inhibited tumor growth in a dose-dependent manner[6]. ML-792 (150, 200mg/kg) was subcutaneously injected into mice bearing HCT-116 cell xenografts, which inhibited tumor growth in a dose-dependent manner[7].
References:
[1] He X, Riceberg J, Soucy T, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor[J]. Nature chemical biology, 2017, 13(11): 1164-1171.
[2] Connolly J G, Plant L D. SUMO regulation of ion channels in health and disease[J]. Physiology, 2025, 40(2).
[3] Celen A B, Sahin U. Sumoylation on its 25th anniversary: mechanisms, pathology, and emerging concepts[J]. The FEBS journal, 2020, 287(15): 3110-3140.
[4] Sahin U, de Thé H, Lallemand-Breitenbach V. Sumoylation in physiology, pathology and therapy[J]. Cells, 2022, 11(5): 814.
[5] Deng Y, Chen Y, Gao S, et al. RREB1-mediated SUMOylation enhancement promotes chemoresistance partially by transcriptionally upregulating UBC9 in colorectal cancer[J]. Frontiers in Pharmacology, 2024, 15: 1381860.
[6] Jin X, Yin H, Bao J, et al. ML792 inhibits growth and TGF-β1-induced EMT of osteosarcoma cells via TGF-β1/Smad and PI3K/AKT pathways[J]. All Life, 2022, 15(1): 1222-1235.
[7] 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 cancer[J]. Journal of medicinal chemistry, 2021, 64(5): 2501-2520.
ML-792是一种特异性的小泛素样修饰物（SUMO）活化酶（SAE）抑制剂，能够抑制SAE/SUMO1和 SAE/SUMO2，IC50分别为3nM和11nM[1]。SUMO蛋白通路能够通过使原位靶蛋白的功能、半衰期和伙伴关系多样化，控制一系列重要的生物过程，包括细胞死亡、增殖、分化、代谢和信号转导[2]。ML-792通常用于研究SUMO化修饰在癌症、神经退行性疾病和病毒感染中的作用[3, 4]。
在体外，ML-792（0, 1, 5μM）处理5-FU耐药细胞系（HCT-8/5-FU细胞）12-16天，显著减少了细胞的菌落形成数量，逆转了细胞的5-FU耐药性[5]。
在体内，ML-792（50, 100mg/kg）通过腹腔注射治疗HOS细胞异种移植小鼠，以剂量依赖性方式抑制了小鼠体内肿瘤的生长[6]。ML-792（150, 200mg/kg）通过皮下注射治疗HCT-116细胞异种移植小鼠，以剂量依赖性方式抑制了小鼠体内肿瘤的生长[7]。