A focused library of protein tyrosine phosphatase inhibitors

Anthony B Comeau; David A Critton; Rebecca Page; Christopher T Seto

doi:10.1021/jm100528p

A focused library of protein tyrosine phosphatase inhibitors

J Med Chem. 2010 Sep 23;53(18):6768-72. doi: 10.1021/jm100528p.

Authors

Anthony B Comeau¹, David A Critton, Rebecca Page, Christopher T Seto

Affiliation

¹ Department of Chemistry, Brown University, 324 Brook Street, Box H, Providence, Rhode Island 02912, USA.

PMID: 20731359
DOI: 10.1021/jm100528p

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Bacterial Outer Membrane Proteins / antagonists & inhibitors
Bacterial Outer Membrane Proteins / chemistry
Keto Acids / chemical synthesis*
Keto Acids / chemistry
Models, Molecular
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / chemistry
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors
Protein Tyrosine Phosphatases / antagonists & inhibitors*
Protein Tyrosine Phosphatases / chemistry
Small Molecule Libraries
Structure-Activity Relationship
Yersinia pestis / enzymology

Substances

Bacterial Outer Membrane Proteins
Keto Acids
Small Molecule Libraries
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatase, Non-Receptor Type 2
Protein Tyrosine Phosphatases
yopH protein, Yersinia