Low Molecular Weight-Protein Tyrosine Phosphatase (LMW-PTP) isoform B (IFB) has been found to be over expressed in many forms of aggressive cancer and has become a target for inhibition. Competitive inhibition of LMW-PTP IFB by known inhibitor pyridoxal-5’-phosphate (PLP) shows a strong inhibition constant (Ki = 7.6 µM at pH 5.0); however, PLP is a cofactor for many other enzymes. In silico screening and in vitro testing identified NSC107022 (Ki = 10.8 ± 1.0) from the National Cancer Institute’s Diversity Set II as a lead compound for optimization as a LMW-PTP IFB inhibitor. Utilizing NSC107022’s galloyl group, compound libraries of aromatic alcohols and amines were connected (ester and amide linkages, respectively) and screened in silico. Compounds yielding top docking scores (most negative) were synthesized and tested in vitro.

Identification, synthesis, and biological activity of galloyl nhibitors of human low molecular weight protein tyrosine phosphatase

249th National Meeting (2015)

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