title: Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors.
abstract: As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50)=9.2μM (compound 38). The structure-activity relationship was also discussed.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Qiao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
authors.forename: Donghua
authors.initials: D
authors.lastname: Wen
authors.forename: Yaxue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Meng
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.forename: Yingli
authors.initials: Y
authors.lastname: Wu
authors.forename: Huchen
authors.initials: H
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: D011480:Protease Inhibitors; D025841:Small Ubiquitin-Related Modifier Proteins