2i03
From Proteopedia
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|PDB= 2i03 |SIZE=350|CAPTION= <scene name='initialview01'>2i03</scene>, resolution 2.400Å | |PDB= 2i03 |SIZE=350|CAPTION= <scene name='initialview01'>2i03</scene>, resolution 2.400Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=AXD:2-[4-({2-[(2S,5R)-2-(AMINOMETHYL)-5-ETHYNYLPYRROLIDIN-1-YL]-2-OXOETHYL}AMINO)-4-METHYLPIPERIDIN-1-YL]ISONICOTINIC ACID'>AXD</scene> | + | |LIGAND= <scene name='pdbligand=AXD:2-[4-({2-[(2S,5R)-2-(AMINOMETHYL)-5-ETHYNYLPYRROLIDIN-1-YL]-2-OXOETHYL}AMINO)-4-METHYLPIPERIDIN-1-YL]ISONICOTINIC+ACID'>AXD</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2g5p|2G5P]], [[2g5t|2G5T]], [[2g63|2G63]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i03 OCA], [http://www.ebi.ac.uk/pdbsum/2i03 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2i03 RCSB]</span> | ||
}} | }} | ||
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[[Category: Longenecker, K L.]] | [[Category: Longenecker, K L.]] | ||
[[Category: Madar, D J.]] | [[Category: Madar, D J.]] | ||
| - | [[Category: AXD]] | ||
[[Category: enzyme]] | [[Category: enzyme]] | ||
[[Category: serine peptidase]] | [[Category: serine peptidase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:37:53 2008'' |
Revision as of 00:37, 31 March 2008
| |||||||
| , resolution 2.400Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||
| Related: | 2G5P, 2G5T, 2G63
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human dipeptidyl peptidase 4 (DPP IV) with potent alkynyl cyanopyrrolidine (ABT-279)
Overview
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.
About this Structure
2I03 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes., Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM, J Med Chem. 2006 Oct 19;49(21):6416-20. PMID:17034148
Page seeded by OCA on Mon Mar 31 03:37:53 2008
