2i03
From Proteopedia
(New page: 200px<br /> <applet load="2i03" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i03, resolution 2.400Å" /> '''Crystal structure ...) |
Revision as of 15:34, 15 February 2008
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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 with as ligand. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 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 Fri Feb 15 17:34:21 2008
