2p8s
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Molecular modeling was used to design a rigid analog of sitagliptin 1. The | + | Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin., Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Apr 2 | + | Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin., Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Jun 15;17(12):3384-7. Epub 2007 Apr 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17433672 17433672] |
[[Category: Dipeptidyl-peptidase IV]] | [[Category: Dipeptidyl-peptidase IV]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: structure-based design]] | [[Category: structure-based design]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:27:05 2008'' |
Revision as of 16:27, 21 February 2008
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Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor
Overview
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile.
About this Structure
2P8S 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
Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin., Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Jun 15;17(12):3384-7. Epub 2007 Apr 2. PMID:17433672
Page seeded by OCA on Thu Feb 21 18:27:05 2008
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Biftu, T. | Scapin, G. | 417 | NA | NAG | Alpha/beta | Beta-propeller | Dimer | Structure-based design
