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1nz7

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==Overview==
==Overview==
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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.
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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==
==Disease==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Abad-Zapatero, C.]]
[[Category: Abad-Zapatero, C.]]
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[[Category: Ballaron, S.J.]]
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[[Category: Ballaron, S J.]]
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[[Category: Hajduk, P.J.]]
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[[Category: Hajduk, P J.]]
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[[Category: Hutchins, C.W.]]
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[[Category: Hutchins, C W.]]
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[[Category: Jirousek, M.R.]]
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[[Category: Jirousek, M R.]]
[[Category: Liu, G.]]
[[Category: Liu, G.]]
[[Category: Lubben, T.]]
[[Category: Lubben, T.]]
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[[Category: Oost, T.K.]]
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[[Category: Oost, T K.]]
[[Category: Pei, Z.]]
[[Category: Pei, Z.]]
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[[Category: Stashko, M.A.]]
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[[Category: Stashko, M A.]]
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[[Category: Szczepankiewicz, B.G.]]
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[[Category: Szczepankiewicz, B G.]]
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[[Category: Trevillyan, J.M.]]
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[[Category: Trevillyan, J M.]]
[[Category: Xin, Z.]]
[[Category: Xin, Z.]]
[[Category: 901]]
[[Category: 901]]
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[[Category: protein tyrosine phosphatase fold]]
[[Category: protein tyrosine phosphatase fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:31:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:11:37 2008''

Revision as of 12:11, 21 February 2008


1nz7, resolution 2.40Å

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

Contents

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 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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