Selective Protein Tyrosine Phosphatase 1B Inhibitors: Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands
- 25 June 2003
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (16) , 3437-3440
- https://doi.org/10.1021/jm034088d
Abstract
Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.Keywords
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