ML297

Description: ML297 is a truly potent and selective GIRK channel agonist with IC50 values are 160, 887 and 914 nM for GIRK1/2, GIRK1/4 and GIRK1/3 respectively. ML297 exhibits no effect on GIRK2, GIRK2/3, Kir2.1 and Kv7.4 channels, and has minimal effect on a panel of other ion channels, receptors and transporters. The G-protein activated, inward-rectifying potassium (K(+)) channels, 'GIRKs', are a family of ion channels (Kir3.1-Kir3.4) that has been the focus of intense research interest for nearly two decades. GIRKs are comprised of various homo- and heterotetrameric combinations of four different subunits.ML297 is active in two in vivo models of epilepsy, a disease where up to 40% of patients remain with symptoms refractory to present treatments. The development of ML297 represents a truly significant advancement in our ability to selectively probe GIRK's role in physiology as well as providing the first tool for beginning to understand GIRK's potential as a target for a diversity of therapeutic indications such as epileptics.

References: ACS Chem Neurosci. 2013 Sep 18; 4(9):1278-86; Biomed Pharmacother. 2018 May; 101:362-370.