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Identifying potent, selective protein tyrosine phosphatase inhibitors from a library of Au(I) complexes.

ABSTRACT: Therapeutic inhibition of protein tyrosine phosphatase activity is a compelling yet challenging approach to the treatment of human disease. Toward this end, a library of 40 gold complexes with the general formula R(3)P-Au-Cl was screened to identify novel inhibitors of PTP activity. The most promising inhibitor obtained for the lymphoid tyrosine phosphatase LYP, (2-pyridine)(Ph(2))P-Au-Cl, is one of the most potent and selective LYP inhibitors identified to date with an IC(50) of 1.5 +/- 0.3 microM, 10-fold selectivity for LYP over PTP-PEST, HePTP, and CD45 in vitro, and activity in cellular studies as well.

SUBMITTER: Karver MR

PROVIDER: S-EPMC2801581 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Identifying potent, selective protein tyrosine phosphatase inhibitors from a library of Au(I) complexes.

Karver Mark R MR Krishnamurthy Divya D Kulkarni Rhushikesh A RA Bottini Nunzio N Barrios Amy M AM

Journal of medicinal chemistry 20091101 21

Therapeutic inhibition of protein tyrosine phosphatase activity is a compelling yet challenging approach to the treatment of human disease. Toward this end, a library of 40 gold complexes with the general formula R(3)P-Au-Cl was screened to identify novel inhibitors of PTP activity. The most promising inhibitor obtained for the lymphoid tyrosine phosphatase LYP, (2-pyridine)(Ph(2))P-Au-Cl, is one of the most potent and selective LYP inhibitors identified to date with an IC(50) of 1.5 +/- 0.3 mic ...[more]

PMID: 19888762

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