Low molecular weight protein tyrosine phosphatase (LMW-PTP), is an 18 kDa acid phosphatase with two unique isoforms (IFA and IFB). It is ubiquitous and active in the regulation of many important cell proliferation pathways including JAK-STAT, PDGF, and EPHA2. IFA overexpression is observed in early cancer cell proliferation, and reduced expression of IFA in later stages of cancer has been found to contribute to cell migration through the RhoA pathway. Isoform specific inhibitors of LMW-PTP could prove to have therapeutic value by controlling dysregulation of this key enzyme. Using in silico methods the National Cancer Institute (NCI) Diversity Set III (1597 compounds) was screened for compounds with similar docking scores to pyridoxal-5’-phosphate (PLP), a known inhibitor of LMW PTP with a competitive inhibitor dissociation constant Kis of 7.6 µM. The NCI compounds with comparable or better docking scores were tested via bioassays on IFA, after which inhibition constants were determined via IgorPro software. Three of these compounds demonstrated significant inhibition (Kis&lt; 75µM) for IFA.

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

253rd National Meeting (2017)

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