title: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman, Jordan. mutasem@ju.edu.jo
authors.forename: Mutasem O
authors.initials: MO
authors.lastname: Taha
authors.forename: Yasser
authors.initials: Y
authors.lastname: Bustanji
authors.forename: Amal G
authors.initials: AG
authors.lastname: Al-Bakri
authors.forename: Al-Motassem
authors.initials: AM
authors.lastname: Yousef
authors.forename: Waleed A
authors.initials: WA
authors.lastname: Zalloum
authors.forename: Ihab M
authors.initials: IM
authors.lastname: Al-Masri
authors.forename: Naji
authors.initials: N
authors.lastname: Atallah
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases