Structure-based virtual screening approach to the discovery of novel PTPMT1 phosphatase inhibitors

Dual-specificity protein 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 IC50 values ranging from 0.7 to 17.3 mu M. 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. (C) 2011 Elsevier Ltd. All rights reserved.This work was supported by Grant No. K11061 from the Korea Institute of Oriental Medicine and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Education, Science, and Technology (2010-0012646)