Discovery of new potent human protein tyrosine phosphatase inhibitors via pharmacophore and QSAR analysis followed by in silico screening

Abstract A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h-PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of physicochemical descriptors and pharmacophore hypothesis that yield consistent QSAR equation of good predictive potential ( r = 0.87 , F -statistic = 69.13 , r BS 2 = 0.76 , r LOO 2 = 0.68 ) . The validity of the QSAR equation and the associated pharmacophoric hypothesis was experimentally established by the identification of five new h-PTP 1B inhibitors retrieved from the National Cancer Institute (NCI) database.