| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
TRPM8
M8-B targets the transient receptor potential melastatin 8 (TRPM8) channel as a potent and selective antagonist. It blocks activation of TRPM8 by cold temperatures, icilin, and menthol. In vitro IC50 values: 7.8 nM for cold-induced activation, 26.9 nM for icilin-induced activation, and 64.3 nM for menthol-induced activation. The compound displays no effect at other TRP channels with IC50 >20 mM, indicating high selectivity for TRPM8. M8-B is used to investigate the role of TRPM8 in regulating body temperature and cold-induced thermogenesis. |
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| ln Vitro |
M8-B (0-100 µM) decreases maximal Ca2+ uptake in a dose-dependent manner, hence inhibiting TRPM8 channel activity [1].
In vitro studies demonstrate that M8-B is a potent transient receptor potential melastatin-8 (TRPM8) antagonist. It blocks cold-induced and TRPM8 agonist-induced TRPM8 channel activation. The compound shows IC50 values of 7.8 nM for cold-induced activation, 26.9 nM for icilin-induced activation, and 64.3 nM for menthol-induced activation. M8-B displays no effect at other TRP channels with IC50 >20 mM, demonstrating high selectivity. It has been used in thermoregulation research to investigate the role of TRPM8 in regulating body temperature. The compound blocks activation by cold, icilin, or menthol in vitro. |
| ln Vivo |
In rats and mice, M8-B (6 mg/kg; iv or ip) lowers deep body temperature[1].
In vivo studies show that M8-B decreases deep body temperature in wild-type mice and rats. The compound has no effect on body temperature in TRPM8 knockout (KO) mice, confirming that its effects are mediated through TRPM8. M8-B has been used to investigate the role of TRPM8 in regulating body temperature, confirming its ability to inhibit cold-induced thermogenesis. The compound has also been studied for therapeutic efficiency in a mouse model of severe dry eye disease (DED) induced by excision of extra-orbital lacrimal and Harderian glands. It may be used to induce therapeutic hypothermia, which is an effective treatment in cardiac arrest. |
| Enzyme Assay |
For TRPM8 channel binding and functional assays, cells expressing TRPM8 channels (e.g., HEK293 cells) are cultured and loaded with calcium-sensitive fluorescent dyes. M8-B is dissolved in DMSO and diluted in assay buffer to varying concentrations. Cells are treated with the compound and TRPM8 activation is induced by cold stimulation (10-25°C), icilin, or menthol. Calcium flux is measured using fluorescence plate readers. IC50 values are calculated from dose-response curves. For selectivity assays, the compound is tested against other TRP channels. Assays are performed in replicate with appropriate vehicle controls and positive controls (e.g., known TRPM8 antagonists). IC50 values: cold 7.8 nM, icilin 26.9 nM, menthol 64.3 nM.
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| Cell Assay |
For in vitro cellular assays, cells expressing TRPM8 channels (e.g., HEK293 cells or primary sensory neurons) are cultured in appropriate media under standard conditions (37°C, 5% CO2). M8-B is dissolved in DMSO and diluted in culture medium to desired concentrations (typically nM range). Cells are treated with compound for specified durations. TRPM8 channel activity is assessed by measuring intracellular calcium flux using fluorescent indicators upon cold, icilin, or menthol stimulation. Cell viability and cytotoxicity can also be assessed. Each concentration is tested in replicate wells with vehicle controls and positive controls. IC50 values: 7.8 nM (cold), 26.9 nM (icilin), 64.3 nM (menthol).
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| Animal Protocol |
Animal/Disease Models: Trpm8+/+ rats and mice[1]
Doses: 6 mg/kg Route of Administration: Iv or ip Experimental Results: diminished deep body temperature (T(b)) in Trpm8+/+ rats and mice, but not in Trpm8−/− mice. For in vivo animal studies, M8-B is typically administered via intraperitoneal (i.p.) injection in appropriate formulations. In thermoregulation studies, wild-type and TRPM8 KO mice or rats are treated with compound and deep body temperature is monitored using rectal probes or telemetry. In dry eye disease models, mice undergo excision of extra-orbital lacrimal and Harderian glands, followed by treatment with M8-B. Tear production and corneal damage are assessed. Dosing regimens vary by study objective. Blood and tissue samples may be collected for pharmacokinetic analysis. All procedures follow institutional animal care and use committee guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of M8-B are characteristic of a small-molecule TRPM8 antagonist. The compound has a molecular weight of 432.96, formula C22H25ClN2O3S, and CAS number 883976-12-3. Storage: typically at -20°C for powder; in solvent at -80°C. The compound is soluble in DMSO and other organic solvents. It exists as a hydrochloride salt form. The compound has been used in thermoregulation research in mice and rats. Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are not extensively reported in publicly available sources. The compound is stable at room temperature for short periods.
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| Toxicity/Toxicokinetics |
According to available safety information, M8-B is intended for research use only and not for human therapeutic applications. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. The compound decreases body temperature in animal models, which should be considered in experimental design. No clinical toxicity data are available.
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| References | |
| Additional Infomation |
M8-B is a potent and selective TRPM8 antagonist with IC50 values of 7.8 nM (cold), 26.9 nM (icilin), and 64.3 nM (menthol). It blocks cold-induced and TRPM8 agonist-induced TRPM8 channel activation and displays no effect at other TRP channels with IC50 >20 mM. The compound decreases deep body temperature in wild-type mice and rats but has no effect in TRPM8 KO mice. It has been used in dry eye disease models and thermoregulation research. The compound is for research use only with no clinical development or regulatory approvals reported.
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| Molecular Formula |
C22H25CLN2O3S
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| Molecular Weight |
432.96
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| Exact Mass |
432.127
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| CAS # |
883976-12-3
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| PubChem CID |
69316632
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
29
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| Complexity |
473
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=CC(=C1)CN(CCN)C(=O)C2=CC=CS2)OCC3=CC=CC=C3.Cl
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| InChi Key |
FMQJBHACRTZLME-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N2O3S.ClH/c1-26-20-14-18(9-10-19(20)27-16-17-6-3-2-4-7-17)15-24(12-11-23)22(25)21-8-5-13-28-21;/h2-10,13-14H,11-12,15-16,23H2,1H3;1H
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| Chemical Name |
N-(2-aminoethyl)-N-[(3-methoxy-4-phenylmethoxyphenyl)methyl]thiophene-2-carboxamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 250 mg/mL (577.42 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.80 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 20.8 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: ≥ 2.08 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3097 mL | 11.5484 mL | 23.0968 mL | |
| 5 mM | 0.4619 mL | 2.3097 mL | 4.6194 mL | |
| 10 mM | 0.2310 mL | 1.1548 mL | 2.3097 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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