title: Discovery of novel, potent, selective and cellular active ADC type PTP1B inhibitors via fragment-docking-oriented de novel design.
abstract: Fragment-docking-oriented de novel design for both the catalytic site and the C phosphotyrosine binding site led to the discovery of novel scaffold and chemical easy N-(2,5-diethoxy-phenyl)-methanesulfonamide based phosphotyrosine mimetics that when incorporated into ureas are high potent and selective inhibitors of protein tyrosine phosphatase 1B. Among them, compound 15 was shown to be the most potent PTP1B inhibitor with great selectivity over the highly homologous T-cell protein tyrosine phosphatase.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China. Electronic address: ylduyjs@163.com.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ling
authors.affiliation: Brunswick Laboratories (China), 5 Xing Han Road, Suzhou 215021, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China. Electronic address: qyli1234@163.com.
authors.forename: Qunyi
authors.initials: Q
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Insulin signaling; N-(2,5-Diethoxy-phenyl)-methanesulfonamide; Protein tyrosine phosphatase 1B inhibitor; Type 2 diabetes mellitus