2IIT

Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor

Summary for 2IIT

• Entry DOI: 10.2210/pdb2iit/pdb
• Related: 2IIV
• Descriptor: Dipeptidyl peptidase 4 soluble form, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: hydrolase; alpha/beta; beta-propeller; dimer, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 174945.83

Authors

Scapin, G.,Biftu, T.,Weber, A.E. (deposition date: 2006-09-28, release date: 2006-11-28, Last modification date: 2024-10-30)

Primary citation

Biftu, T.,Feng, D.,Qian, X.,Liang, G.B.,Kieczykowski, G.,Eiermann, G.,He, H.,Leiting, B.,Lyons, K.,Petrov, A.,Sinha-Roy, R.,Zhang, B.,Scapin, G.,Patel, S.,Gao, Y.D.,Singh, S.,Wu, J.,Zhang, X.,Thornberry, N.A.,Weber, A.E.
(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Bioorg.Med.Chem.Lett., 17:49-52, 2007

PubMed Abstract: Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

PubMed: 17055272
DOI: 10.1016/j.bmcl.2006.09.099

Experimental method

X-RAY DIFFRACTION (2.35 Å)