title: Identification of new inhibitors for low molecular weight protein tyrosine phosphatase isoform B.
abstract: The National Cancer Institute Diversity Set II (1356 compounds) and Diversity Set III (1597 compounds) were screened via in silico methods as potential inhibitors of low molecular weight protein tyrosine phosphatase (LWM-PTP) isoform B (EC 3.1.3.48). Those candidates that demonstrated comparable or better docking scores than that of pyridoxal 5'-phosphate (PLP), one of the most potent known inhibitors of LMW-PTP with a competitive inhibitor dissociation constant (Kis) of 7.6μM (pH 5.0), were analyzed via in vitro kinetic assays against LMW-PTP isoform B. While none of the compounds tested in vitro was significantly better that PLP, five compounds showed comparable inhibition. These five compounds are very diverse in structure and represent new therapeutic leads for inhibition of this isozyme.
authors.affiliation: Department of Chemistry, College of Saint Benedict, Saint John's University, St. Joseph, MN 56374, United States.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Seiler
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Richards
authors.forename: Henry V
authors.initials: HV
authors.lastname: Jakubowski
authors.forename: Edward J
authors.initials: EJ
authors.lastname: McIntee
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000201:enzymology; D011487:Protein Conformation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Cancer; Computational biology; Drug discovery; Inhibitors; LMW-PTP