1x70
From Proteopedia
(New page: 200px<br /> <applet load="1x70" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x70, resolution 2.10Å" /> '''HUMAN DIPEPTIDYL PE...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 16: | Line 15: | ||
[[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.]] | ||
| Line 31: | Line 30: | ||
[[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'' |
Revision as of 13:51, 21 February 2008
|
HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR
Overview
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
1X70 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
(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: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes., Kim D, Wang L, Beconi M, Eiermann GJ, Fisher MH, He H, Hickey GJ, Kowalchick JE, Leiting B, Lyons K, Marsilio F, McCann ME, Patel RA, Petrov A, Scapin G, Patel SB, Roy RS, Wu JK, Wyvratt MJ, Zhang BB, Zhu L, Thornberry NA, Weber AE, J Med Chem. 2005 Jan 13;48(1):141-51. PMID:15634008
Page seeded by OCA on Thu Feb 21 15:51:46 2008
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Beconi, M. | Eiermann, G J. | Fisher, M H. | He, H. | Hickey, G J. | Kim, D. | Leiting, B. | Lyons, K. | Wang, L. | 715 | NA | NAG | Alpha/beta | Beta-propeller | Dimer
