Selective protein tyrosine phosphatase 1B inhibitors: Targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands

被引：108

作者：

Liu, G

Xin, ZL

Liang, H

Abad-Zapatero, C

Hajduk, PJ

Janowick, DA

Szczepankiewicz, BG

Pei, ZH

Hutchins, CW

Ballaron, SJ

Stashko, MA

Lubben, TH

Berg, CE

Rondinone, CM

Trevillyan, JM

Jirousek, MR

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Metab Dis Res, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Global Pharmaceut Res & Dev, Adv Technol, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 16期

关键词：

D O I：

10.1021/jm034088d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3437 / 3440

页数：4

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