title: A focused library of protein tyrosine phosphatase inhibitors.
abstract: Protein tyrosine phosphatases such as PTP1B and YopH are potential targets for the development of therapeutic agents against a variety of pathological conditions including diabetes, obesity, and infection by the bacterium Yersinia pestis. A focused library of bidentate α-ketoacid-based inhibitors has been screened against several tyrosine phosphatases. Compound 2a has IC(50) values of 43 and 220 nM against YopH and PTP1B, respectively, and shows a 30-fold selectivity for PTP1B over the closely related phosphatase TCPTP.
authors: Department of Chemistry, Brown University, 324 Brook Street, Box H, Providence, Rhode Island 02912, USA.
authors: Anthony B
authors: AB
authors: Comeau
authors: David A
authors: DA
authors: Critton
authors: Rebecca
authors: R
authors: Page
authors: Christopher T
authors: CT
authors: Seto
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D015010:Yersinia pestis / Q000201:enzymology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D007651:Keto Acids; D054852:Small Molecule Libraries; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia