2iiv
From Proteopedia
(New page: 200px<br /> <applet load="2iiv" size="450" color="white" frame="true" align="right" spinBox="true" caption="2iiv, resolution 2.15Å" /> '''Human dipeptidyl pe...) |
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| - | [[Image:2iiv.gif|left|200px]]<br /> | + | [[Image:2iiv.gif|left|200px]]<br /><applet load="2iiv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2iiv" size=" | + | |
caption="2iiv, resolution 2.15Å" /> | caption="2iiv, resolution 2.15Å" /> | ||
'''Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor'''<br /> | '''Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 | + | Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. |
==About this Structure== | ==About this Structure== | ||
| - | 2IIV 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 NAG and 565 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] Full crystallographic information is available from [http:// | + | 2IIV 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=NAG:'>NAG</scene> and <scene name='pdbligand=565:'>565</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IIV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Biftu, T.]] | [[Category: Biftu, T.]] | ||
[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
| - | [[Category: Weber, A | + | [[Category: Weber, A E.]] |
[[Category: 565]] | [[Category: 565]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: hydrolase; alpha/beta; beta-propeller; dimer]] | [[Category: hydrolase; alpha/beta; beta-propeller; dimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:53:10 2008'' |
Revision as of 15:53, 21 February 2008
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Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor
Overview
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.
About this Structure
2IIV is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Full crystallographic information is available from OCA.
Reference
(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoro ethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes., Biftu T, Feng D, Qian X, Liang GB, Kieczykowski G, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Scapin G, Patel S, Gao YD, Singh S, Wu J, Zhang X, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Jan 1;17(1):49-52. Epub 2006 Oct 5. PMID:17055272
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