ML67-33
目录号 : GC38555
ML67-33 是一种对温度和机械敏感的 K2P 通道的选择性激活剂。ML67-33 快速可逆地激活 K2P2.1 (TREK-1)，在无细胞体系和 HEK293 细胞中 EC50 分别为 36.3 μM 和 9.7 μM。
Cas No.:1443290-89-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ML67-33 is a selective activator of temperature- and mechano-sensitive K2P channels. ML67-33 rapidly and reversibly affects K2P2.1 (TREK-1) with EC50s of 36.3 μM and 9.7 μM in cell-free and HEK293 cells, respectively[1].
ML67-33 activates K2P channels and mutants with EC50s of 21.8±1.3 μM, 49.4±1.1 μM, 30.2±1.4 μM, and 27.3±1.2 μM for K2P2.1 (TREK-1) W275S, K2P2.1 (TREK-1)-3G, K2P10.1 (TREK-2), K2P4.1 (TRAAK), respectively[1].
[1]. Bagriantsev SN, et al. A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels. ACS Chem Biol. 2013 Aug 16;8(8):1841-51.
| Cas No. | 1443290-89-8 | SDF | |
| Canonical SMILES | CC1(C)C2=C(C=CC(Cl)=C2)N(CCC3=NN=NN3)C4=CC=C(Cl)C=C14 | ||
| 分子式 | C18H17Cl2N5 | 分子量 | 374.27 |
| 溶解度 | DMSO : 100 mg/mL (267.19 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6719 mL | 13.3593 mL | 26.7187 mL |
| 5 mM | 0.5344 mL | 2.6719 mL | 5.3437 mL |
| 10 mM | 0.2672 mL | 1.3359 mL | 2.6719 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels
ACS Chem Biol 2013 Aug 16;8(8):1841-51.PMID:23738709DOI:PMC3747594
K2P (KCNK) potassium channels generate "leak" potassium currents that strongly influence cellular excitability and contribute to pain, somatosensation, anesthesia, and mood. Despite their physiological importance, K2Ps lack specific pharmacology. Addressing this issue has been complicated by the challenges that the leak nature of K2P currents poses for electrophysiology-based high-throughput screening strategies. Here, we present a yeast-based high-throughput screening assay that avoids this problem. Using a simple growth-based functional readout, we screened a library of 106,281 small molecules and identified two new inhibitors and three new activators of the mammalian K2P channel K2P2.1 (KCNK2, TREK-1). By combining biophysical, structure-activity, and mechanistic analysis, we developed a dihydroacridine analogue, ML67-33, that acts as a low micromolar, selective activator of temperature- and mechano-sensitive K2P channels. Biophysical studies show that ML67-33 reversibly increases channel currents by activating the extracellular selectivity filter-based C-type gate that forms the core gating apparatus on which a variety of diverse modulatory inputs converge. The new K2P modulators presented here, together with the yeast-based assay, should enable both mechanistic and physiological studies of K2P activity and facilitate the discovery and development of other K2P small molecule modulators.