1x70: Difference between revisions
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New page: left|200px<br /> <applet load="1x70" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x70, resolution 2.10Å" /> '''HUMAN DIPEPTIDYL PE... |
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[[Image:1x70.gif|left|200px]]<br /> | [[Image:1x70.gif|left|200px]]<br /><applet load="1x70" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1x70" size=" | |||
caption="1x70, resolution 2.10Å" /> | caption="1x70, resolution 2.10Å" /> | ||
'''HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR'''<br /> | '''HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of | A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin -7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes. | ||
==About this Structure== | ==About this Structure== | ||
1X70 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, NA and 715 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:// | 1X70 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>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=715:'>715</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=1X70 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Beconi, M.]] | [[Category: Beconi, M.]] | ||
[[Category: Eiermann, G | [[Category: Eiermann, G J.]] | ||
[[Category: Fisher, M | [[Category: Fisher, M H.]] | ||
[[Category: He, H.]] | [[Category: He, H.]] | ||
[[Category: Hickey, G | [[Category: Hickey, G J.]] | ||
[[Category: Kim, D.]] | [[Category: Kim, D.]] | ||
[[Category: Leiting, B.]] | [[Category: Leiting, B.]] | ||
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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 15:51:46 2008'' | ||
