BL-1249 is a selective and potent non-steroidal potassium channel activator with anti-inflammatory activity that activates K2P2.1 (TREK-1) and K2P10.1 (TREK-2).

TREK1:5.5 μM (EC50), Smooth muscle cells (SMCs):21.0 μM (Human, EC50), TREK2:8.0 μM (EC50)

Evaluated by a decrease in fluorescence of the voltage-sensitive dye bis(1,2-dibutylbarbituric acid)trimethine oxonol (EC50 = 1.26 +/- 0.6 μM) or direct electrophysiological measurements (EC50 = 1.49 +/- 0.08 μM), BL-1249 demonstrates concentration-dependent membrane depolarization in cultured human bladder smooth muscle cells[2]. Patch clamp experiments indicate that, akin to a diverse range of other TREK subfamily gating signals, BL-1249 stimulates a selective screening 'C-type' gate that controls K2P functionality. BL-1249 exhibits selectivity within the TREK subfamily, activating K2P2.1 (TREK-1) and K2P10.1 (TREK-2) approximately 10 times more actively than K2P4.1 (TRAAK). Studies on mutants and K2P2.1 (TREK-1)/K2P4.1 (TRAAK) chimeras highlight the critical role of the C-terminal tail in the action of BL-1249, and identify the M2/M3 transmembrane helix interface as a key site of BL-1249 selectivity[1].

In an anesthetized rat model, BL-1249 (1 mg/kg i.v.) decreased the number of isovolumic contractions, without significantly affecting blood pressure. Thus, BL-1249 behaves as a potassium channel activator that exhibits bladder versus vascular selectivity both in vitro and in vivo[2].