| Description | 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). |
| In vitro | 通过电压敏感染料双(1,2-二丁基巴比妥酸)三甲基氧氮烯酮的荧光减少(EC50 = 1.26 +/- 0.6 μM)或直接电生理测量(EC50 = 1.49 +/- 0.08 μM)评估，BL-1249 表现出对培养的人膀胱肌细胞的浓度依赖性膜去极化[2]。贴片钳实验表明，与其他TREK亚家族门控信号的多样范围相似，BL-1249刺激了控制K2P功能的选择性筛选' C型' 门。BL-1249在TREK亚家族中显示出选择性，激活K2P2.1(TREK-1)和K2P10.1(TREK-2)比激活K2P4.1(TRAAK)更具活性高出约10倍。对突变体和K2P2.1(TREK-1)/K2P4.1(TRAAK)嵌合体的研究突出了C-末端尾部在BL-1249作用中的关键作用，并确定了M2/M3跨膜螺旋界面作为BL-1249选择性的关键位点[1]。 |
| In vivo | 在麻醉的大鼠模型中，BL-1249(1 mg/kg 静脉注射)减少了等容性收缩的数量，但并未显著影响血压。因此，BL-1249表现出作为钾通道激活剂的特性，在体外和体内均表现出膀胱与血管的选择性。 |
| Target activity | TREK2:8.0 μM (EC50), Smooth muscle cells (SMCs):21.0 μM (Human, EC50), TREK1:5.5 μM (EC50) |
| molecular weight | 291.35 |
| Molecular formula | C17H17N5 |
| CAS | 18200-13-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 30 mg/mL (102.97 mM), Sonication is recommended. |
| References | 1. Pope L, et al. Protein and Chemical Determinants of BL-1249 Action and Selectivity for K2P Channels. ACS Chem Neurosci. 2018 Dec 19;9(12):3153-3165. 2. Tertyshnikova S, et al. BL-1249 [(5,6,7,8-tetrahydro-naphthalen-1-yl)-[2-(1H-tetrazol-5-yl)-phenyl]-amine]: a putative potassium channel opener with bladder-relaxant properties. J Pharmacol Exp Ther. 2005 Apr;313(1):250-9. 3. Iwaki Y, et al. Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249. Bioorg Med Chem Lett. 2019 Jul 1;29(13):1601-1604. |