ML365

ML365 (CAS No.: 947914-18-3) is a potent and selective small-molecule inhibitor of the two-pore domain potassium channel TASK1 (KCNK3), widely utilized as a pharmacological probe to investigate the physiological and pathological roles of TASK1-mediated background potassium currents. It exhibits high inhibitory activity in the nanomolar range, with reported IC50 values around 4 nM in thallium flux fluorescence assays and approximately 16 nM in automated electrophysiological measurements, demonstrating consistent potency across assay platforms. ML365 shows strong selectivity for TASK1 over closely related potassium channels, including TASK3, as well as minimal activity against other ion channels such as Kir2.1, KCNQ2, and hERG at micromolar concentrations, supporting its utility in dissecting TASK1-specific signaling without significant off-target interference. In addition, ML365 has been reported to exhibit moderate antagonistic activity against metabotropic glutamate receptor mGluR5 in the low micromolar range, which may be considered in experimental design. Functionally, inhibition of TASK1 by ML365 modulates membrane potential and cellular excitability, making it valuable for studies in neurophysiology, cardiopulmonary research, and ion channel pharmacology. In vitro and cellular studies typically employ concentration ranges spanning low nanomolar to micromolar levels depending on assay sensitivity and experimental objectives, and it is commonly applied in target validation, ion channel characterization, and early-stage drug discovery efforts.