title: Identification of SENP1 inhibitors through in silico screening and rational drug design.
abstract: The small ubiquitin-related modifier (SUMO)-specific proteases (SENPs) catalyze the deconjugation of SUMO from their substrate proteins. SENP1 which is the most studied isoform is closely related to many cancers such as prostate cancer and colon cancer, thus representing a potential therapeutic target for cancer treatment. In the present study, we identified eleven SENP1 inhibitors representing a variety of scaffolds through in silico screening. Based on these scaffolds, a series of new compounds were designed and synthesized in order to improve their SENP1 inhibitory potency. As a result, compounds with IC50 as low as 3.5 μM (compound 13m) were obtained and a preliminary structure-activity relationship was discussed.
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Yaxue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Jianchen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. Electronic address: hczhou@sjtu.edu.cn.
authors.forename: Huchen
authors.initials: H
authors.lastname: Zhou
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D010450:Endopeptidases / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D010450:Endopeptidases
keywords: Cancer; In silico screening; Rational design; SENP1 inhibitor