INHIBITION OF SHP2/PTPN11 PROTEIN TYROSINE PHOSPHATASE BY NSC-87877, NSC-117199 AND THEIR ANALOGS

摘要

Compounds and associated methods for inhibiting a protein tyrosine phosphatase. By a combination of experimental and virtual screenings of the NCI Diversity Set chemical library, NSC-87877 and NSC-117199 have been identified as Shp2 PTP inhibitors. Significantly, NSC-87877 is active in cell-based assays and has no detectable off-target effects in the EGF-stimulated Erkl/2 activation pathway. Additionally, a number of analogs of NSC-1 17199 have been produced. These analogs exhibit enhanced protein tyrosine phosphatase inhibition and arc found to be potent and/or selectiv e inhibitors of Shp l and/or Shp2 protein tyrosine phosphatases.