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Purity: ≥98%
ML213 (formerly known as CID-3111211) is a potent and selective activator/opener of Kv7.2 (KCNQ2) and Kv7.4 (KCNQ4) channels which enhances Kv7.2 and Kv7.4 channels with EC50 of 230 and 510 nM, respectively. ML213 shows more than 80-fold selectivity for Kv7.2 (KCNQ2) and Kv7.4 (KCNQ4) versus a large battery of related potassium channels such as KV7.1, KV7.3 and KV7.5 in a thallium-based fluorescence assay, it also can afford modest brain levels. ML213, as a potent vasorelaxant in different blood vessels, may have the potential to be developed as therapeutics for various smooth muscle disorders.
| ln Vitro |
With an EC50 of 0.8 ± 0.3 µM, ML213 (100 nM-30 µM) raises maximum conductance to a peak of 212% ± 27% of control. The deactivation rates of Kv7.4 currents are 4.6 times lower at 10 µM of ML213 in the voltage range of -130 mV to -90 mV. Strong and efficient homomeric Kv7.5 channel activator ML213 is overexpressed in A7r5 cells. With an EC50 of 0.7 ± 0.2 µM, ML213 increases the maximal conductance of Kv7.5 channels. Additionally, Kv7.5 current deactivation rates are averagely reduced by 5.9 times by ML213 (10 µM). On heteromeric Kv7.4/7.5 channels, ML213 had comparable effects: a maximal conductance increase of 204% ± 11% with an EC50 of 1.1 ± 0.6 µM and a maximal negative shift of the activation curve of 34.2 ± 3.3 mV with an EC50 of 3.8 ± 1.2 µM[1]. Vasorelaxation is induced by ML213 in various precontracted rat blood arteries. Additionally, mesenteric artery smooth muscle cells are hyperpolarized by ML213 (10 μM)[2]. For KCNQ2 activation, ML213 generates a concentration-dependent change in the V1/2 with a peak shift of 37.4 mV and an EC50 of 340 ± 70 nM[3].
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| References |
[1]. Brueggemann LI, et al. Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673. Mol Pharmacol. 2014 Sep;86(3):330-41.
[2]. Jepps TA, et al. Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370. Br J Pharmacol. 2014 Oct;171(19):4413-24. [3]. Yu H, et al. Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011 Oct 19;2(10):572-577 |
| Molecular Formula |
C17H23NO
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| Molecular Weight |
257.38
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| CAS # |
489402-47-3
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(C1CC2CCC1C2)NC3=C(C)C=C(C)C=C3C
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (10.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (10.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (10.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8853 mL | 19.4265 mL | 38.8531 mL | |
| 5 mM | 0.7771 mL | 3.8853 mL | 7.7706 mL | |
| 10 mM | 0.3885 mL | 1.9427 mL | 3.8853 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
ML213 induced a concentration-dependent enhancement of the Kv7.4 current accompanied by negative shift of the activation curve and prolonged Kv7.4 current deactivation.Mol Pharmacol.2014 Sep;86(3):330-41. |
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ML213 induced a concentration-dependent enhancement of Kv7.5 current accompanied by negative shift of the activation curve and decreased Kv7.5 current deactivation rate.Mol Pharmacol.2014 Sep;86(3):330-41. |
ML213 induced a concentration-dependent enhancement of Kv7.4/7.5 current accompanied by negative shift of the activation curve and decreased Kv7.4/7.5 current deactivation rate.Mol Pharmacol.2014 Sep;86(3):330-41. |
Summary of ML213-induced concentration-dependent negative shift of activation curves, increased maximal conductance, and decreased Kv7.4, Kv7.5, and Kv7.4/7.5 current deactivation rates.Mol Pharmacol.2014 Sep;86(3):330-41. |
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Comparison of effects of 10µM ML213 on wild-type Kv7.5 and retigabine-insensitive mutant Kv7.5 W235L.Mol Pharmacol.2014 Sep;86(3):330-41. |
Comparison of the effects of 10µM ML213 on wild-type Kv7.4 and retigabine-insensitive mutant Kv7.4 W242L.Mol Pharmacol.2014 Sep;86(3):330-41. |
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