ML 792

• CAT Number: I012899
• CAS Number: 1644342-14-2
• Molecular Formula: C21H23BrN6O5S
• Molecular Weight: 551.42
• Purity: ≥95%
• Synonyms: ML 792;((1R,2S,4R)-4-((5-(1-(3-bromobenzyl)-1H-pyrazole-3-carbonyl)pyrimidin-4-yl)amino)-2-hydroxycyclopentyl)methyl sulfamate
• Target: SUMO-activating enzyme

ML-792 (CAT: I012899) is a novel and potent inhibitor of SUMO-activating enzyme (SAE), which is involved in the process of SUMOylation. By selectively blocking SAE enzyme activity, ML-792 effectively inhibits the overall SUMOylation process. SUMOylation is a post-translational modification that plays a crucial role in various cellular processes, including protein stability, subcellular localization, and protein-protein interactions. By decreasing total SUMOylation, ML-792 has shown promising anti-cancer properties, including the inhibition of cancer cell proliferation. The inhibition of SAE by ML-792 represents a potential therapeutic strategy for targeting SUMOylation pathways in cancer treatment.

Reference

1. Nat Chem Biol. 2017 Nov;13(11):1164-1171. doi: 10.1038/nchembio.2463. Epub 2017
Sep 11.

Probing the roles of SUMOylation in cancer cell biology by using a selective SAE
inhibitor.

He X(1), Riceberg J(1), Soucy T(1), Koenig E(1), Minissale J(1), Gallery M(1),
Bernard H(1), Yang X(1), Liao H(1), Rabino C(1), Shah P(1), Xega K(1), Yan ZH(1),
Sintchak M(1), Bradley J(1), Xu H(1), Duffey M(1), England D(1), Mizutani H(1),
Hu Z(1), Guo J(1), Chau R(1), Dick LR(1), Brownell JE(1), Newcomb J(1), Langston
S(1), Lightcap ES(1), Bence N(1), Pulukuri SM(1).

Author information:
(1)Oncology Drug Discovery Unit, Takeda Pharmaceuticals International Co.,
Cambridge, Massachusetts, USA.

Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein
functions by post-translational modification. However, a potent and selective
inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a
mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in
cellular assays. ML-792 selectively blocks SAE enzyme activity and total
SUMOylation, thus decreasing cancer cell proliferation. Moreover, we found that
induction of the MYC oncogene increased the ML-792-mediated viability effect in
cancer cells, thus indicating a potential application of SAE inhibitors in
treating MYC-amplified tumors. Using ML-792, we further explored the critical
roles of SUMOylation in mitotic progression and chromosome segregation.
Furthermore, expression of an SAE catalytic-subunit (UBA2) S95N M97T mutant
rescued SUMOylation loss and the mitotic defect induced by ML-792, thus
confirming the selectivity of ML-792. As a potent and selective SAE inhibitor,
ML-792 provides rapid loss of endogenously SUMOylated proteins, thereby
facilitating novel insights into SUMO biology.