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ID: ALA2010696

Journal: Bioorg Med Chem Lett

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

Authors: Brocklehurst KJ, Broo A, Butlin RJ, Brown HS, Clarke DS, Davidsson Ö, Goldberg K, Groombridge SD, Kelly EE, Leach A, McKerrecher D, O'Donnell C, Poucher S, Schofield P, Scott JS, Teague J, Westgate L, Wood MJ.

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.

CiteXplore: 22061639

DOI: 10.1016/j.bmcl.2011.10.033