2P8S

Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor

Summary for 2P8S

• Entry DOI: 10.2210/pdb2p8s/pdb
• Related: 1X70
• Descriptor: DIPEPTIDYL PEPTIDASE IV SOLUBLE FORM, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: alpha/beta, beta-propeller, dimer, structure-based design, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 174961.88

Authors

Scapin, G.,Biftu, T. (deposition date: 2007-03-23, release date: 2007-05-22, Last modification date: 2024-10-16)

Primary citation

Biftu, T.,Scapin, G.,Singh, S.,Feng, D.,Becker, J.W.,Eiermann, G.,He, H.,Lyons, K.,Patel, S.,Petrov, A.,Sinha-Roy, R.,Zhang, B.,Wu, J.,Zhang, X.,Doss, G.A.,Thornberry, N.A.,Weber, A.E.
Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin
Bioorg.Med.Chem.Lett., 17:3384-3387, 2007

PubMed Abstract: 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.

PubMed: 17433672
DOI: 10.1016/j.bmcl.2007.03.095

Experimental method

X-RAY DIFFRACTION (2.2 Å)