BL-1249

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BL-1249 是一种非甾体抗炎剂 (NSAID) 和钾通道激活剂，可有效激活 K2P2.1 (TREK-1) 和 K2P10.1 (TREK-2)，EC50 值分别为 5.5 μM 和 8.0 μM。BL-1249 在细胞外激活了所有 TREK 亚家族成员，但对其他 K2P 亚家族没有影响。BL-1249 对膀胱的选择性 (EC50 为 1.26 μM) 比对血管组织 (EC50 为 21.0 μM) 更高。

BL-1249 is a nonsteroidal anti-inflammatory agent (NSAID) and a potassium channel activator. BL-1249 potently activates K2P2.1 (TREK-1) and K2P10.1 (TREK-2) with EC50 values of 5.5 μM and 8.0 μM, respectively. BL-1249 extracellular application activates all TREK subfamily members but has no effect on other K2P subfamilies. BL-1249 exhibits more selective for the bladder (EC50 of 1.26 μM) than vascular tissue (EC50 of 21.0 μM).

BL-1249 produces a concentration-dependent membrane hyperpolarization of cultured human bladder myocytes, assessed as either a reduction in fluorescence of the voltage-sensitive dye bis-(1,2-dibutylbarbituric acid)trimethine oxonol (EC50 of 1.26 μM) or by direct electrophysiological measurement EC50 of 1.49 μM). BL-1249 produced a concentration-dependent hyperpolarization with an EC50 of 21.0 μM in human aortic smooth muscle cells.In in vitro organ bath experiments, BL-1249 produces a concentration-dependent relaxation of 30 mM KCl-induced contractions in rat bladder strips (EC50 of 1.12 μM), yet has no effect on aortic strips up to the highest concentration tested (10 μM). The bladder relaxation produced by BL-1249 is partially blocked by Ba2+ (1 and 10 mM).BL-1249 is a selective agonist of the TREK subfamily when applied extracellularly, having preferential action on K2P2.1(TREK-1) and K2P10.1(TREK-2) over K2P4.1(TRAAK) and establish that its mechanism of action relies on gating at the selectivity filter C-type gate.

BL-1249 (1 mg/kg) inhibits isovolumic bladder contractions in vivo. The short duration of the effect of BL-1249 on bladder contraction ( 30 min) is likely due to a fast elimination half-life of the compound after i.v. administration (0.69 h). BL-1249 (1 mg/kg) has little effect on mean arterial blood pressure, an observation again consistent with the in vitro bladder to vascular relaxant selectivity.

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Cell Cycle/DNA Damage

Potassium Channel

Potassium Channel

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18200-13-0

291.35

C17H17N5

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 50 mg/mL (171.61 mM; 超声助溶 (<60°C)

C1CCc2c(C1)cccc2Nc1ccccc1-c1nnn[nH]1

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(-20℃)

With Ice Pack

≥ 2 years