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Description: LY2812223 is a novel, highly potent, functionally selective mGlu2 receptor agonist with mGlu2 binding affinity (Ki) of 144 nM and 156 nM for mGlu2 and mGlu3, respectively. Identification of orthosteric mGlu(2/3) receptor agonists capable of discriminating between individual mGlu2 and mGlu3 subtypes has been highly challenging owing to the glutamate-site sequence homology between these proteins. Evaluation of LY2812223 in a rat model responsive to mGlu2 receptor activation coupled with a measure of central drug disposition provides evidence that this molecule engages and activates central mGlu2 receptors in vivo.
References: J Med Chem. 2015 Sep 24; 58(18):7526-48.
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