Solid-phase assembly and in situ screening of protein tyrosine phosphatase inhibitors

Rajavel Srinivasan; Lay Pheng Tan; Hao Wu; Shao Q Yao

doi:10.1021/ol8006875

Solid-phase assembly and in situ screening of protein tyrosine phosphatase inhibitors

Org Lett. 2008 Jun 5;10(11):2295-8. doi: 10.1021/ol8006875. Epub 2008 May 6.

Authors

Rajavel Srinivasan¹, Lay Pheng Tan, Hao Wu, Shao Q Yao

Affiliation

¹ Department of Chemistry and Biological Sciences, NUS MedChem Program of the Office of Life Sciences, National University of Singapore, Singapore.

PMID: 18457404
DOI: 10.1021/ol8006875

Abstract

A highly efficient solid-phase strategy for assembly of small molecule inhibitors against protein tyrosine phosphatase 1B (PTP1B) is described. The method is highlighted by its simplicity and product purity. A 70-member combinatorial library of analogues of a known PTP1B inhibitor has been synthesized, which upon direct in situ screening revealed a potent inhibitor ( Ki = 7.0 microM) against PTP1B.

Publication types

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

MeSH terms

Amides / chemistry
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Protein Tyrosine Phosphatases / antagonists & inhibitors*
Time Factors

Substances

Amides
Enzyme Inhibitors
Protein Tyrosine Phosphatases