title: Structure-based virtual screening approach to the discovery of novel PTPMT1 phosphatase inhibitors.
abstract: Dual-specificity protein tyrosine phosphatase localized to mitochondrion 1 (PTPMT1) has recently proved to be a promising therapeutic target for the treatment of type II diabetes. Herein we report the first example for a successful application of the structure-based virtual screening to identify the novel inhibitors of human PTPMT1. These inhibitors were computationally screened for having desirable physicochemical properties as a drug candidate and reveal a high potency with IC(50) values ranging from 0.7 to 17.3μM. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the antidiabetic activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTPMT1 are addressed in detail.
authors: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143 747, Republic of Korea.
authors: Hwangseo
authors: H
authors: Park
authors: Song Yi
authors: SY
authors: Kim
authors: Ayoung
authors: A
authors: Kyung
authors: Tae-Sung
authors: TS
authors: Yoon
authors: Seong Eon
authors: SE
authors: Ryu
authors: Dae Gwin
authors: DG
authors: Jeong
mesh_terms: D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D051059:PTEN Phosphohydrolase