Biochem/physiol Actions

Orignially characterized as an mGluR5 negative allosteric modulator (IC50 = 1.35 µM, E_max = 3.82% of Glu E_max; rat mGluR5 HEK293A cells), ML365 is now better known as selective two-pore potassium (K2P) channel TASK1 (K2P3.1; KCNK3) inhibitor with 100- and 62-fold selectivity over TASK3 (K2p9.1; KCNK9), respectively, by thellium flux (rat TASK1/TASK3 CHO cell IC50 = 4/390 nM) and QPatch assay (rat TASK1/TASK3 CHO cell IC50 = 16/990 nM). ML365 is employed in the range from 40 nM to 20 µM. Selective TASK1 blockage is achieved at the lower end of the concentration range, while TASK3 activity can also be inhibited at the high end of the range.