ML365Potent and selective TASK-1 channel blocker CAS# 947914-18-3 |
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Quality Control & MSDS
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| Cas No. | 947914-18-3 | SDF | Download SDF |
| PubChem ID | 46785920 | Appearance | Powder |
| Formula | C22H20N2O3 | M.Wt | 360.41 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (277.46 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-methoxy-N-[3-[(3-methylbenzoyl)amino]phenyl]benzamide | ||
| SMILES | CC1=CC=CC(=C1)C(=O)NC2=CC(=CC=C2)NC(=O)C3=CC=CC=C3OC | ||
| Standard InChIKey | UTAJHKSGYJSZBR-UHFFFAOYSA-N | ||
| Standard InChI | 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) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent and selective TASK-1 (K2P3.1/KCNK3) channel blocker (IC50 values are 4 and 390 nM at TASK-1 and TASK-3, respectively). Displays little or no inhibition at Kir2.1, voltage-gated potassium channels, KCNQ2 and KV11.1 (hERG). |
ML365 Dilution Calculator
ML365 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7746 mL | 13.8731 mL | 27.7462 mL | 55.4924 mL | 69.3654 mL |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | 11.0985 mL | 13.8731 mL |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 mL | 5.5492 mL | 6.9365 mL |
| 50 mM | 0.0555 mL | 0.2775 mL | 0.5549 mL | 1.1098 mL | 1.3873 mL |
| 100 mM | 0.0277 mL | 0.1387 mL | 0.2775 mL | 0.5549 mL | 0.6937 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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ML365 is a novel selective small molecule inhibitor of TASK1(KCNK3) with IC50 of 4 nM(thallium influx fluorescent assay) and 16 nM(automated electrophysiology assay).
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A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type-1 cells.[Pubmed:30284397]
Physiol Rep. 2018 Sep;6(19):e13876.
Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BKC a ) potassium channels which leads to membrane depolarization, voltage-gated Ca-entry, and neurosecretion. Here, we investigate the effects of pharmacological inhibitors on TASK channel activity and [Ca(2+) ]i -signaling in isolated neonatal rat type-1 cells. PK-THPP inhibited TASK channel activity in cell attached patches by up to 90% (at 400 nmol/L). A1899 inhibited TASK channel activity by 35% at 400 nmol/L. PK-THPP, A1899 and Ml 365 all evoked a rapid increase in type-1 cell [Ca(2+) ]i . These [Ca(2+) ]i responses were abolished in Ca(2+) -free solution and greatly attenuated by Ni(2+) (2 mM) suggesting that depolarization and voltage-gated Ca(2+) -entry mediated the rise in [Ca(2+) ]i. Doxapram (50 mumol/L), a respiratory stimulant, also inhibited type-1 cell TASK channel activity and increased [Ca(2+) ]i. . We also tested the effects of combined inhibition of BKC a and TASK channels. TEA (5 mmol/L) slightly increased [Ca(2+) ]i in the presence of PK-THPP and A1899. Paxilline (300 nM) and iberiotoxin (50 nmol/L) also slightly increased [Ca(2+) ]i in the presence of A1899 but not in the presence of PK-THPP. In general [Ca(2+) ]i responses to TASK inhibitors, alone or in combination with BKC a inhibitors, were smaller than the [Ca(2+) ]i responses evoked by hypoxia. These data confirm that TASK channel inhibition is capable of evoking membrane depolarization and robust voltage-gated Ca(2+) -entry but suggest that this, even with concomitant inhibition of BKC a channels, may be insufficient to account fully for the [Ca(2+) ]i -response to hypoxia.
pH-dependent inhibition of K(2)P3.1 prolongs atrial refractoriness in whole hearts.[Pubmed:26729267]
Pflugers Arch. 2016 Apr;468(4):643-54.
In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.1 (KCNK3), together with K2P9.1 (KCNK9), could represent novel drug targets for the treatment of atrial fibrillation (AF). However, it is unknown whether these findings in isolated cells translate to the whole heart. The purposes of this study were to investigate the expression levels of KCNK3 and KCNK9 in human hearts and two relevant rodent models and determine the antiarrhythmic potential of K2P3.1 inhibition in isolated whole-heart preparations. By quantitative PCR, we found that KCNK3 is predominantly expressed in human atria whereas KCNK9 was not detectable in heart human tissue. No differences were found between patients in AF or sinus rhythm. The expression in guinea pig heart resembled humans whereas rats displayed a more uniform expression of KCNK3 between atria and ventricle. In voltage-clamp experiments, ML365 and A293 were found to be potent and selective inhibitors of K2P3.1, but at pH 7.4, they failed to prolong atrial APD and refractory period (effective refractory period (ERP)) in isolated perfused rat and guinea pig hearts. At pH 7.8, which augments K2P3.1 currents, pharmacological channel inhibition produced a significant prolongation of atrial ERP (11.6 %, p = 0.004) without prolonging ventricular APD but did not display a significant antiarrhythmic effect in our guinea pig AF model (3/8 hearts converted on A293 vs 0/7 hearts in time-matched controls). These results suggest that when K2P3.1 current is augmented, K2P3.1 inhibition leads to atrial-specific prolongation of ERP; however, this ERP prolongation did not translate into significant antiarrhythmic effects in our AF model.
Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold.[Pubmed:25017033]
Bioorg Med Chem Lett. 2014 Aug 15;24(16):3968-73.
TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC50=16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay.
