ML402 |
Catalog No.GC31062
One-Click Copy Product Info
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ML402, a thiophene-carboxamide, is a selective K2P2.1(TREK-1) and K2P10.1(TREK-2) activator.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 298684-44-3
Sample solution is provided at 25 µL, 10mM.
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ML402 is a selective TREK-1 activator.
Xenopus oocyte two-electrode voltage-clamp measurements show that ML335 and ML402 activate K2P2.1 and K2P10.1 but not K2P4.1(14.3±2.7 μM, K2P2.1-ML335; 13.7±7.0 μM, K2P2.1-ML402; 5.2±0.5 μM, K2P10.1-ML335; and 5.9±1.6 μM, K2P10.1-ML402). The K2P modulator pocket has a single difference among TREK subfamily members at the cation-π interaction position, K2P2.1 Lys271, which is also a lysine in K2P10.1 but a glutamine in K2P4.1.Swapping the Lys271 equivalent between K2P2.1 and K2P4.1 results in a clear phenotype reversal for ML335 and M402 activation. K2P2.1 (K271Q) is insensitive to ML335 and ML402, whereas K2P4.1 (Q258K) responds to both with a similar EC50 to K2P2.1 (14.3±2.7 μM, K2P2.1-ML335; 16.2±3.0 μM, K2P4.1(Q258K)-ML335; 13.7±7.0 μM, K2P2.1-ML402; 13.6±1.5 μM, K2P4.1 (Q258K)-ML402) but with a lower magnitude response than K2P2.1[1].
[1]. Lolicato M, et al. K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017 Jul 20;547(7663):364-368.
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Kinase experiment: |
K2P2.1cryst ML335 and ML402 complex crystals grow in the same conditions as K2P2.1cryst, but the protein is incubated for at least 1 h with 2.5 mM of activator (including ML 402) before setting the crystal plates. ML335 and ML402 are insoluble in aqueous solutions, so they are dissolved in 100% DMSO at a concentration of 500 mM. Then each compound is diluted 1:100 in SEC buffer to 5 mM concentration, giving a milky solution. This solution is mixed 1:1 to K2P2.1cryst previously concentrating to 12 mg/mL. The K2P2.1cryst ML402 mixture results in a clear solution, while the mixture with ML335 is slightly milky. The samples are briefly centrifuged in a table-top centrifuge (10,000×g) to remove any insoluble material before setting the crystal plates. Dose-response experiments are carried by first preparing a DMSO stock solution of each activator (including ML402) at a concentration of 100 mM. Owing to the low solubility of the compounds the highest test concentrations in recording solution are 100 μM and 80 μM for ML335 and ML402, respectively. Other concentrations are prepared by serial dilutions of the 100 μM solution in recording buffer supplementing with 0.1% DMSO[1]. |
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References: [1]. Lolicato M, et al. K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017 Jul 20;547(7663):364-368. |
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| Cas No. | 298684-44-3 | SDF | |
| Canonical SMILES | O=C(C1=CC=CS1)NCCOC2=CC=C(Cl)C=C2C | ||
| Formula | C14H14ClNO2S | M.Wt | 295.78 |
| Solubility | DMSO : 150 mg/mL (507.13 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3809 mL | 16.9045 mL | 33.8089 mL |
| 5 mM | 676.2 μL | 3.3809 mL | 6.7618 mL |
| 10 mM | 338.1 μL | 1.6904 mL | 3.3809 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)