2fjp: Difference between revisions
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New page: left|200px<br /> <applet load="2fjp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fjp, resolution 2.40Å" /> '''Human dipeptidyl pe... |
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[[Image:2fjp.gif|left|200px]]<br /> | [[Image:2fjp.gif|left|200px]]<br /><applet load="2fjp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2fjp" size=" | |||
caption="2fjp, resolution 2.40Å" /> | caption="2fjp, resolution 2.40Å" /> | ||
'''Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor'''<br /> | '''Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
A series of beta-substituted biarylphenylalanine amides were synthesized | A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes. | ||
==About this Structure== | ==About this Structure== | ||
2FJP 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 S14 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:// | 2FJP 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=S14:'>S14</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=2FJP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Becker, J | [[Category: Becker, J W.]] | ||
[[Category: Patel, S | [[Category: Patel, S B.]] | ||
[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: dimer]] | [[Category: dimer]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:22:05 2008'' | ||
