1onz
From Proteopedia
(New page: 200px<br /> <applet load="1onz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1onz, resolution 2.40Å" /> '''Oxalyl-aryl-Amino B...) |
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| - | [[Image:1onz.gif|left|200px]]<br /> | + | [[Image:1onz.gif|left|200px]]<br /><applet load="1onz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1onz" size=" | + | |
caption="1onz, resolution 2.40Å" /> | caption="1onz, resolution 2.40Å" /> | ||
'''Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b'''<br /> | '''Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key | + | Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1ONZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 968 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http:// | + | 1ONZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=968:'>968</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ONZ OCA]. |
==Reference== | ==Reference== | ||
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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: Fesik, S | + | [[Category: Fesik, S W.]] |
| - | [[Category: Hadjuk, P | + | [[Category: Hadjuk, P J.]] |
| - | [[Category: Hutchins, C | + | [[Category: Hutchins, C W.]] |
| - | [[Category: Janowich, D | + | [[Category: Janowich, D A.]] |
| - | [[Category: Jirousek, M | + | [[Category: Jirousek, M R.]] |
[[Category: Liang, H.]] | [[Category: Liang, H.]] | ||
[[Category: Liu, G.]] | [[Category: Liu, G.]] | ||
[[Category: Lubben, T.]] | [[Category: Lubben, T.]] | ||
| - | [[Category: Mika, A | + | [[Category: Mika, A K.]] |
[[Category: Pei, Z.]] | [[Category: Pei, Z.]] | ||
| - | [[Category: Stashko, M | + | [[Category: Stashko, M A.]] |
| - | [[Category: Szczepankiewicz, B | + | [[Category: Szczepankiewicz, B G.]] |
| - | [[Category: Trevillyan, J | + | [[Category: Trevillyan, J M.]] |
[[Category: Xin, Z.]] | [[Category: Xin, Z.]] | ||
| - | [[Category: Zinker, B | + | [[Category: Zinker, B A.]] |
[[Category: 968]] | [[Category: 968]] | ||
[[Category: oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor]] | [[Category: oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor]] | ||
[[Category: protein tyrosine phosphatase]] | [[Category: protein tyrosine phosphatase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:19:56 2008'' |
Revision as of 12:19, 21 February 2008
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Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b
Contents |
Overview
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1ONZ 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
Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B., Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR, J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781
Page seeded by OCA on Thu Feb 21 14:19:56 2008
Categories: Homo sapiens | Protein-tyrosine-phosphatase | Single protein | Abad-Zapatero, C. | Ballaron, S J. | Fesik, S W. | Hadjuk, P J. | Hutchins, C W. | Janowich, D A. | Jirousek, M R. | Liang, H. | Liu, G. | Lubben, T. | Mika, A K. | Pei, Z. | Stashko, M A. | Szczepankiewicz, B G. | Trevillyan, J M. | Xin, Z. | Zinker, B A. | 968 | Oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor | Protein tyrosine phosphatase
