1ph0
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Abad-Zapatero, C.]] | [[Category: Abad-Zapatero, C.]] | ||
| - | [[Category: Ballaron, S | + | [[Category: Ballaron, S J.]] |
[[Category: Hajduk, P.]] | [[Category: Hajduk, P.]] | ||
| - | [[Category: Hutchins, C | + | [[Category: Hutchins, C W.]] |
[[Category: Janowick, D.]] | [[Category: Janowick, D.]] | ||
[[Category: Liang, H.]] | [[Category: Liang, H.]] | ||
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[[Category: salicylic acid moiety at the second site]] | [[Category: salicylic acid moiety at the second site]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:28:41 2008'' |
Revision as of 12:28, 21 February 2008
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Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1PH0 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
Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands., Liu G, Xin Z, Liang H, Abad-Zapatero C, Hajduk PJ, Janowick DA, Szczepankiewicz BG, Pei Z, Hutchins CW, Ballaron SJ, Stashko MA, Lubben TH, Berg CE, Rondinone CM, Trevillyan JM, Jirousek MR, J Med Chem. 2003 Jul 31;46(16):3437-40. PMID:12877578
Page seeded by OCA on Thu Feb 21 14:28:41 2008
Categories: Homo sapiens | Protein-tyrosine-phosphatase | Single protein | Abad-Zapatero, C. | Ballaron, S J. | Hajduk, P. | Hutchins, C W. | Janowick, D. | Liang, H. | Liu, G. | Pei, Z. | Szczepankiewicz, B. | Xin, Z. | 418 | Oxalyl-aryl-benzoic acid compound inhibitor | Protein tyrosine phosphatase 1b | Salicylic acid moiety at the second site
