ML297 (VU 0456810) is a potent, selective, CNS-penetrant small molecule agonist of GIRK1/2 channel with EC50 of 160 nM.
ML297 shows a preference for the GIRK1/GIRK2 subunit combination compared to GIRK1/GIRK4 and is inactive on GIRK2/GIRK3 and a number of other potassium channels.
ML297 selectively activates recombinant neuronal GIRK channels containing the GIRK1 subunit in a manner that requires PIP2.
ML297 decreases anxiety-related behavior without sedative or addictive liabilities in mice.
