Activator of K2P2.1 (TREK-1) and K2P10.1 (TREK-2) channels
ML402 is a selective activator of K2P2.1 (TREK-1) and K2P10.1 (TREK-2) potassium channels. It was used to determine a cryptic selectivity filter binding site of the K2P2.1 (TREK-1) channel, designated the K2P modulator pocket. This binding pocket stabilizes an active "leak-mode" conformation, binding small-molecule activators that restrict the mobility of the selectivity filter and surrounding structure.
Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel
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