CAY10786 is an antagonist of G protein-coupled receptor 52 (GPR52; IC₅₀= 0.63 µM).¹It reduces mutant huntingtin (mHTT) protein levels in STHdh^Q7/Q111cells, a heterozygousin vitromodel of Huntington’s disease, in a concentration-dependent manner. CAY10786 (3 µM) reduces apoptosis induced by growth factor deprivation in primary striatal neurons isolated from the heterozygous Hdh^Q7/Q140mouse model of Huntington’s disease. It decreases striatal levels of soluble and insoluble mHTT, as well as increases the latency to fall in the rotarod test, in the homozygous Hdh^Q140mouse model of Huntington’s disease, when administered at a dose of 5 mg/kg.

1.Wang, C., Zhang, Y.-F., Guo, S., et al.GPR52 antagonist reduces huntingtin levels and ameliorates Huntington’s disease-related phenotypesJ. Med. Chem.64(2)941-957(2021)