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Discovery, optimisation and in vivo evaluation of novel GPR119 agonists
Katy J Brocklehurst1, Anders Broo, Roger J Butlin
1Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
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.
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