Referenced in: none

Automatically associated channels: Kv11.1

Title: Discovery, optimisation and in vivo evaluation of novel GPR119 agonists.

Authors: Katy J Brocklehurst, Anders Broo, Roger J Butlin, Hayley S Brown, David S Clarke, Öjvind Davidsson, Kristin Goldberg, Sam D Groombridge, Elizabeth E Kelly, Andrew Leach, Darren McKerrecher, Charles O'Donnell, Simon Poucher, Paul Schofield, James S Scott, Joanne Teague, Leanne Westgate, Matt J M Wood

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Dec 15 , 21, 7310-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22061639

Abstract
GPR119 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. During a programme aimed at developing agonists of the GPR119 receptor, we identified compounds that were potent with reduced hERG liabilities, that had good pharmacokinetic properties and that displayed excellent glucose-lowering effects in vivo. However, further profiling in a GPR119 knock-out (KO) mouse model revealed that the biological effects were not exclusively due to GPR119 agonism, highlighting the value of transgenic animals in drug discovery programs.