title: Identification of novel PTPRQ phosphatase inhibitors based on the virtual screening with docking simulations.
abstract: Protein tyrosine phosphatase receptor type Q (PTPRQ) is an unusual PTP that has intrinsic dephosphorylating activity for various phosphatidyl inositides instead of phospho-tyrosine substrates. Although PTPRQ was known to be involved in the pathogenesis of obesity, no small-molecule inhibitor has been reported so far. Here we report six novel PTPRQ inhibitors identified with computer-aided drug design protocol involving the virtual screening with docking simulations and enzyme inhibition assay. These inhibitors exhibit moderate potencies against PTPRQ with the associated IC50 values ranging from 29 to 86 μM. Because the newly discovered inhibitors were also computationally screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further development by structure-activity relationship studies to optimize the antiobestic activities. Structural features relevant to the stabilization of the inhibitors in the active site of PTPRQ are addressed in detail.
authors: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Korea. hspark@sejong.ac.kr.
authors: Hwangseo
authors: H
authors: Park
authors: Keum Ran
authors: KR
authors: Yu
authors: Bonsu
authors: B
authors: Ku
authors: Bo Yeon
authors: BY
authors: Kim
authors: Seung Jun
authors: SJ
authors: Kim
mesh_terms: D020134:Catalytic Domain; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007295:Inositol Phosphates / Q000378:metabolism; D062105:Molecular Docking Simulation; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; C118500:inositol 3,4,5-trisphosphate; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
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