ML-220

ML-220 is a potent and selective small-molecule activator of the KCNQ2/3 (Kv7.2/Kv7.3) potassium channel, which is responsible for the M-current that regulates neuronal excitability. Discovered through the NIH Molecular Libraries Program at Vanderbilt University, ML-220 acts as a positive allosteric modulator by shifting the voltage-dependence of channel activation toward more hyperpolarized potentials. This enhancement of potassium conductance stabilizes the resting membrane potential and suppresses repetitive neuronal firing. ML-220 is primarily utilized as a pharmacological tool to investigate the role of KCNQ channels in various physiological and pathological states, including epilepsy and neuropathic pain. It offers a distinct chemical scaffold compared to the first-in-class KCNQ opener retigabine, providing a valuable resource for drug discovery efforts targeting neuronal hyperexcitability.

Other names

N-(2,4-difluorophenyl)-1H-pyrazole-3-carboxamide