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spinqualitylabelsall models 1nz7, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

We have previously reported a novel series of oxalyl-aryl-amino benzoic, acid-based, catalytic site-directed, competitive, reversible protein, tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key, intermediates, we utilized a solution phase parallel synthesis approach, and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM), with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through, interacting with a second phosphotyrosine binding site (site 2) in the, close proximity to the catalytic site.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]

About this Structure

1NZ7 is a Single protein structure of sequence from Homo sapiens with 901 as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.

Reference

Potent, selective inhibitors of protein tyrosine phosphatase 1B., Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G, Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891

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