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Purity: ≥98%
ML365 is a potent, novel and selective small molecule inhibitor of the TASK1(KCNK3, a two-pore domain potassium channel). ML365 blocks TASK1 channels in both the thallium influx fluorescent assay (IC50 = 4 nM) and an automated electrophysiology assay (IC50 = 16 nM). Based on potency differences, it possesses more than 60-fold selectivity for inhibition of TASK1 over a closely-related, two-pore domain potassium channel, TASK3. ML365 displays little or no inhibition at 30 μM of more distantly related potassium channels, Kir2.1, potassium voltage-gated channel, KQT-like subfamily, member 2 (KCNQ2), and human ether-a go-go-related gene (hERG). Based on these criteria, ML365 is a best-in-class probe and is a useful pharmacological probe for in vitro studies of TASK1 function and in further studies aimed at developing therapeutic intervention.
| Targets |
ML365 is a selective inhibitor of the KCNK3/TASK1 two - pore potassium channel, with an IC50 of 4 nM in the thallium influx fluorescent assay and 16 nM in the automated electrophysiology assay. It has more than 60 - fold selectivity for inhibiting TASK1 over TASK3 [1]
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| ln Vitro |
ML365 blocks TASK1 channels in a dose - dependent manner. In the thallium influx fluorescent assay, it can inhibit the influx of thallium through TASK1 channels with an IC50 of 4 nM. In an automated electrophysiology assay, the IC50 for blocking TASK1 channels is 16 nM. At a concentration of 30 μM, it has little or no inhibitory effect on Kir2.1, KCNQ2, and hERG potassium channels [1]
In automated electrophysiological studies (IC50 = 16 nM) and thallium influx fluorescence assays (IC50 = 4 nM), ML365 inhibits TASK1 channels [1]. At 30 μM or no inhibitory impact, ML365 has minimal activity against the potassium voltage-gated channel, KQT-like subfamily, member 2 (KCNQ2), human ether-a go-go related gene (hERG), and the distantly related potassium channel Kir2.1 [1]. ML365 does not show acute toxicity in cell-based studies at doses as high as 30 μM [1]. |
| Enzyme Assay |
For the thallium influx fluorescent assay, TASK1 - expressing cells are incubated with thallium ions and a fluorescent dye. Then, different concentrations of ML365 (ranging from low to high) are added, and the fluorescence intensity is measured. The fluorescence intensity is related to the influx of thallium through TASK1 channels, and the IC50 of ML365 can be calculated according to the dose - response curve. For the automated electrophysiology assay, the patch - clamp technique is used to record the current of TASK1 channels. Cells expressing TASK1 channels are clamped at a certain potential, and different concentrations of ML365 are added, and the change of channel current is observed to determine the inhibitory effect of ML365 on TASK1 channels and calculate the IC50 value [1]
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| References | |
| Additional Infomation |
Two - pore domain potassium channels play important roles in regulating cell membrane potential, and TASK1 is one of them. ML365 was obtained by high - throughput fluorescent screening of the Molecular Libraries Small Molecule Repository (MLSMR) library and structure - activity relationship (SAR) analysis of active compounds. It is a novel selective small - molecule inhibitor of TASK1, which can be used as a useful pharmacological probe for in vitro studies of TASK1 function and is helpful for further research on therapeutic interventions [1]
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| Molecular Formula |
C22H20N2O3
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| Molecular Weight |
360.405805587769
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| Exact Mass |
360.147
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| Elemental Analysis |
C, 73.32; H, 5.59; N, 7.77; O, 13.32
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| CAS # |
947914-18-3
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| Related CAS # |
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| PubChem CID |
46785920
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| Appearance |
White to off-white solid powder
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| Density |
1.253±0.06 g/cm3 (20 °C, 760 mmHg)
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| Boiling Point |
429.9±40.0 °C (760 mmHg)
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| LogP |
4.654
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
510
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=C(C)C=CC=1)NC1C=C(NC(C2C(OC)=CC=CC=2)=O)C=CC=1
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| InChi Key |
UTAJHKSGYJSZBR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20N2O3/c1-15-7-5-8-16(13-15)21(25)23-17-9-6-10-18(14-17)24-22(26)19-11-3-4-12-20(19)27-2/h3-14H,1-2H3,(H,23,25)(H,24,26)
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| Chemical Name |
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| Synonyms |
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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: ≥ 3 mg/mL (8.32 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 30.0 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: ≥ 3 mg/mL (8.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7746 mL | 13.8731 mL | 27.7462 mL | |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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.
Control experiment with ethacrynic acid (panel A) and chemical stability of ML365 over 8 h in the presence of a 5-fold concentration of dithiothreitol (panel B).PMID: 24479195 |
Inhibition of thallium signal in TASK1/KCNK3-expressing cells by ML365.
Selectivity of ML365 effect against various potassium channels using fluorescent-based assays.PMID: 24479195 |
Aqueous stability of ML365 over 48 h in 1:1 PBS/acetonitrile.
Selectivity of ML365 effect for TASK1 as compared to TASK3 using QPatch 16X.PMID: 24479195 |
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