2OPH

Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor

Summary for 2OPH

• Entry DOI: 10.2210/pdb2oph/pdb
• Related: 1X70 2FJP 2IIT 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: alpha/beta, beta-propeller, dimer, type 2 diabetes, selective inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 174778.02

Authors

Scapin, G.,Weber, A.E.,Duffy, J.L. (deposition date: 2007-01-29, release date: 2007-05-08, Last modification date: 2024-10-30)

Primary citation

Duffy, J.L.,Kirk, B.A.,Wang, L.,Eiermann, G.J.,He, H.,Leiting, B.,Lyons, K.A.,Patel, R.A.,Patel, S.B.,Petrov, A.,Scapin, G.,Wu, J.K.,Thornberry, N.A.,Weber, A.E.
4-Aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV.
Bioorg.Med.Chem.Lett., 17:2879-2885, 2007

PubMed Abstract: A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.

PubMed: 17350841
DOI: 10.1016/j.bmcl.2007.02.066

Experimental method

X-RAY DIFFRACTION (2.4 Å)