Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design.

Article Details

Citation

Copy to clipboard

Liang GB, Qian X, Biftu T, Singh S, Gao YD, Scapin G, Patel S, Leiting B, Patel R, Wu J, Zhang X, Thornberry NA, Weber AE

Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design.

Bioorg Med Chem Lett. 2008 Jul 1;18(13):3706-10. doi: 10.1016/j.bmcl.2008.05.061. Epub 2008 May 20.

PubMed ID

18524582 [ View in PubMed

]

Abstract

Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4'-[(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]biphenyl-3-carboxamide	Dipeptidyl peptidase 4	IC 50 (nM)	32	N/A	N/A	Details