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Purity: ≥98%
ML402 (ML-402) is a potent and selective activator of TREK-1/-2 and an agonist for OPRM1-OPRD1 (OPRM1: opioid receptor mu 1; OPRD1: delta opioid receptor) heterdimerization. ML402 selectively activates OPRM1-OPRD1 heterodimerization which may have potential use in the treatment of pain and alleviate unwanted effects associated with opiate use. ML402-define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation-π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate 'leak mode' and provide direct evidence for K2P selectivity filter gating.Heteromerization of OPRM1 with OPRD1 leads to the modulation of receptor binding and signaling properties. It has further been shown that the selective activation of the OPRM1-OPRD1 heteromer by a combination of OPRM1 agonist with OPRD1 antagonist can be blocked by antibodies that selectively recognize the heteromer.
| ln Vitro |
ML335 and ML402 activate K2P2.1 and K2P10.1 but not K2P4.1, according to two-electrode voltage-clamp studies on Xenopus oocytes (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). K2P2.1 Lys271, which is likewise a lysine in K2P10.1 but a glutamine in K2P4.1, is the only variation between TREK subfamily members at the cation-π interaction site in the K2P modulator pocket. When the Lys271 equivalent is switched between K2P2.1 and K2P4.1, ML335 and M402 activation exhibit a pronounced phenotypic reversal. K2P4.1 (Q258K) responds to both ML402 and ML335 with a smaller magnitude response than K2P2.1[1], but with an EC50 that is similar 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)[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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| Molecular Formula |
C14H14CLNO2S
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| Molecular Weight |
295.78
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| CAS # |
298684-44-3
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(C1=CC=CS1)NCCOC2=CC=C(Cl)C=C2C
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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: ≥ 2.5 mg/mL (8.45 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 25.0 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: ≥ 2.5 mg/mL (8.45 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 25.0 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 | 3.3809 mL | 16.9045 mL | 33.8089 mL | |
| 5 mM | 0.6762 mL | 3.3809 mL | 6.7618 mL | |
| 10 mM | 0.3381 mL | 1.6904 mL | 3.3809 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.
K2P2.1(TREK-1) structures.Nature.2017 Jul 20;547(7663):364-368 |
K2P2.1(TREK-1) activator interactions.Nature.2017 Jul 20;547(7663):364-368 |
K2P2.1(TREK-1) C-tail and lipid binding sites.Nature.2017 Jul 20;547(7663):364-368 |
K2P2.1(TREK-1) activator function.Nature.2017 Jul 20;547(7663):364-368 |
K2Pactivator responses.Nature.2017 Jul 20;547(7663):364-368 |
K2Pchannel patch clamp recordings.Nature.2017 Jul 20;547(7663):364-368 |
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