title: Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase.
abstract: Protein tyrosine phosphatases (PTPs) play key roles in many physiological processes, including cell proliferation, differentiation, immune responses and neural activities. Inappropriate regulation of the PTP activity could lead to human diseases, such as cancer or diabetes. Functional studies of PTP can be greatly facilitated by chemical probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. Here, we characterize compound E4 as a new class of PTP activity probes. Compound E4 inactivate STEP in a time- and concentration-dependent fashion. Further study showed that compound E4 inhibits a series of PTPs in a time dependent manner, whereas it shows little or no inhibition toward metal dependent protein phosphatases. Collectively, this new identified covalent inhibitor of PTPs has the potential to be developed to an active site Cys directed PTP probes to study the active properties of the PTPs in cell signaling.
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Physiology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Physiology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Kang-Shuai
authors.initials: KS
authors.lastname: Li
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Li
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xu-Ben
authors.initials: XB
authors.lastname: Hou
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Hong-da
authors.initials: HD
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, School of Medicine, Duke University, Durham, NC 27705, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address: rengj@sdu.edu.cn.
authors.forename: Gui-Jie
authors.initials: GJ
authors.lastname: Ren
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. Electronic address: haofangcn@sdu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address: sunjinpeng@sdu.edu.cn.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Sun
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D013844:Thiazoles; D017027:Protein Tyrosine Phosphatases
keywords: Covalent inhibitor; Irreversible; PTP; Probe; STEP