Identification of new inhibitors for low molecular weight protein tyrosine phosphatase isoform B

Authors

Christopher L. Seiler, College of Saint Benedict/Saint John's University
Kyle A. Richards, College of Saint Benedict/Saint John's University
Henry V. Jakubowski, College of Saint Benedict/Saint John's UniversityFollow
Edward J. McIntee, College of Saint Benedict/Saint John's UniversityFollow

Document Type

Article

Publication Date

11-2013

Disciplines

Chemistry | Physical Sciences and Mathematics

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 (K_is) of 7.6 μM (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.

Comments

DOI: 10.1016/j.bmcl.2013.08.079

Recommended Citation

Seiler, C. L.; Richards, K. A.; Jakubowski, H. V.; McIntee, E. J. Identification of new inhibitors for low molecular weight protein tyrosine phosphatase isoform B. Bioorg Med Chem Lett., 2013, 23(21), 5912-5914.