Solid-phase assembly and in situ screening of protein tyrosine phosphatase inhibitors.
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.
Srinivasan
Rajavel
R
Department of Chemistry and Biological Sciences, NUS MedChem Program of the Office of Life Sciences, National University of Singapore, Singapore.
Tan
Lay Pheng
LP
Wu
Hao
H
Yao
Shao Q
SQ
D000577:Amides / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000577:Amides; D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases