title: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Karver
authors.forename: Divya
authors.initials: D
authors.lastname: Krishnamurthy
authors.forename: Rhushikesh A
authors.initials: RA
authors.lastname: Kulkarni
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Amy M
authors.initials: AM
authors.lastname: Barrios
mesh_terms: D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D006046:Gold; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010720:Phosphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000037:antagonists & inhibitors; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology
chemical_list: D056831:Coordination Complexes; D050607:Organogold Compounds; D010720:Phosphines; C545550:chloro(diphenyl-2-pyridylphosphine)gold(I); D006046:Gold; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases