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ID: ALA1153717

Journal: Bioorg Med Chem Lett

Title: Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA.

Authors: Rawls KA, Lang PT, Takeuchi J, Imamura S, Baguley TD, Grundner C, Alber T, Ellman JA.

Abstract: The development of low muM inhibitors of the Mycobacterium tuberculosis phosphatase PtpA is reported. The most potent of these inhibitors (K(i)=1.4+/-0.3 microM) was found to be selective when tested against a panel of human tyrosine and dual-specificity phosphatases (11-fold vs the highly homologous HCPtpA, and >70-fold vs all others tested). Modeling the inhibitor-PtpA complexes explained the structure-activity relationships observed in vitro and revealed further possibilities for compound development.

CiteXplore: 19889539

DOI: 10.1016/j.bmcl.2009.10.090