| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
EC50: 36.3 μM (K2P2.1 (TREK-1)), 9.7 μM (K2P2.1 (TREK-1), in HEK293 cells)[1].
The primary targets of ML67-33 are members of the two-pore domain potassium (K2P) channel family, particularly the temperature- and mechano-sensitive channels TREK-1 (K2P2.1), TREK-2 (K2P10.1), and TRAAK (K2P4.1). It activates K2P2.1 (TREK-1) with EC50s of 36.3 μM in cell-free systems and 9.7 μM in HEK293 cells. The compound also activates K2P2.1 (TREK-1) mutants with EC50s of 21.8 μM (W275S), 49.4 μM (3G), 30.2 μM for K2P10.1 (TREK-2), and 27.3 μM for K2P4.1 (TRAAK). By activating these channels, ML67-33 increases potassium conductance, leading to membrane hyperpolarization and reduced neuronal excitability. |
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| ln Vitro |
K2P2.1 (TREK-1) W275S, K2P2.1 (TREK-1)-3G, K2P10.1 (TREK-2), and K2P4.1 (TRAAK) have EC50 values of 21.8±1.3 μM, 49.4±1.1 μM, 30.2±1.4 μM, and 27.3±1.2 μM, respectively. ML67-33 is known to activate K2P channels and variants.
In vitro, ML67-33 is a selective activator of K2P channels. It rapidly and reversibly affects K2P2.1 (TREK-1) with EC50s of 36.3 μM and 9.7 μM in cell-free and HEK293 cells, respectively. The compound activates K2P channels and various mutants with EC50s of 21.8 μM, 49.4 μM, 30.2 μM, and 27.3 μM for different channel variants. It is typically used in electrophysiological studies to examine channel function. ML67-33 is soluble in DMSO at 100 mg/mL (267.19 mM) with ultrasonic assistance and is stored at -20°C. |
| ln Vivo |
In vivo, ML67-33 is used to study the physiological roles of K2P channels, which are involved in pain perception, mood regulation, and neuroprotection. By activating these channels, ML67-33 can modulate neuronal excitability and influence various physiological processes. The compound has potential applications in research on pain, neurological disorders, and cardiovascular function. However, detailed in vivo efficacy and safety data are not extensively reported in the available literature, and its use is primarily limited to preclinical research settings.
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| Enzyme Assay |
In vitro assays for ML67-33 typically involve measuring K2P channel activity using electrophysiological techniques such as patch-clamp recording in cell lines expressing recombinant K2P channels (e.g., HEK293 cells). The compound is applied to the cells at varying concentrations (typically in the micromolar range), and the resulting changes in potassium current are measured. The EC50 values for channel activation are determined by fitting concentration-response curves. Cell-free assays, such as those using inside-out membrane patches, can also be used to study the direct effects of ML67-33 on channel gating.
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| Cell Assay |
Cellular assays for ML67-33 typically use HEK293 cells transfected with K2P channel constructs. The compound is applied to the cells, and its effects on channel activity are assessed using electrophysiological techniques such as patch-clamp recording. Fluorescent-based membrane potential assays using voltage-sensitive dyes can also be used for higher-throughput screening of channel activity. Cells are treated with ML67-33 at various concentrations (e.g., 1-100 µM), and the changes in membrane potential are measured. The EC50 for channel activation is determined from the concentration-response data.
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| Animal Protocol |
In vivo animal studies for ML67-33 would likely involve the administration of the compound to rodent models to study its effects on pain perception, neuronal excitability, or cardiovascular function. The compound could be administered via intraperitoneal injection, oral gavage, or local injection, depending on the study design. Endpoints would depend on the specific research question and could include behavioral tests (e.g., pain sensitivity assays), electrophysiological recordings, or measurements of physiological parameters such as blood pressure or heart rate. However, specific in vivo study protocols for ML67-33 are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for ML67-33 are not extensively reported in the available literature. The compound has a molecular weight of 374.27 g/mol and is soluble in DMSO at 100 mg/mL. Information concerning product stability, particularly in solution, has rarely been reported. For research purposes, the compound is typically stored as a powder at -20°C. Detailed parameters such as half-life, volume of distribution, and bioavailability are not publicly available and would need to be determined experimentally.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for ML67-33 in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions for handling chemical reagents. The compound is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information. Any potential toxicity would need to be assessed through formal toxicological studies if the compound were to be developed further.
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| References | |
| Additional Infomation |
ML67-33 is a selective activator of temperature- and mechano-sensitive K2P channels. It activates K2P2.1 (TREK-1) with EC50s of 36.3 μM and 9.7 μM in cell-free and HEK293 cells, respectively. The compound has a molecular formula of C18H17Cl2N5 and a molecular weight of 374.27 g/mol. ML67-33 is used in neuroscience and pain research to study the role of K2P channels in neuronal excitability and sensory processing. It is soluble in DMSO at 100 mg/mL and is stored at -20°C.
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| Molecular Formula |
C18H17CL2N5
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|---|---|
| Molecular Weight |
374.267081022263
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| Exact Mass |
373.086
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| CAS # |
1443290-89-8
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| PubChem CID |
86272454
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| Appearance |
White to off-white solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
446
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2=C(C=1)C(C)(C)C1C=C(C=CC=1N2CCC1N=NNN=1)Cl
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| InChi Key |
GQPMJOXQJUGJPG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H17Cl2N5/c1-18(2)13-9-11(19)3-5-15(13)25(8-7-17-21-23-24-22-17)16-6-4-12(20)10-14(16)18/h3-6,9-10H,7-8H2,1-2H3,(H,21,22,23,24)
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| Chemical Name |
2,7-dichloro-9,9-dimethyl-10-[2-(2H-tetrazol-5-yl)ethyl]acridine
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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 |
| 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) |
DMSO: 100 mg/mL (267.19 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.34 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 12.5 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 | 2.6719 mL | 13.3593 mL | 26.7187 mL | |
| 5 mM | 0.5344 mL | 2.6719 mL | 5.3437 mL | |
| 10 mM | 0.2672 mL | 1.3359 mL | 2.6719 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.
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