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| Targets |
TRPM8 antagonist 3 selectively targets the transient receptor potential melastatin 8 (TRPM8) channel, a non-selective cation channel activated by cold temperatures, menthol, and icilin. The compound exhibits potent antagonistic activity with an IC50 value of 11 nM against TRPM8. It demonstrates inhibitory activity against human TRPM8 receptors expressed in HEK293 cells. The compound shows potent IC50 values of 11.0 nM for reducing Ca2+ efflux induced by ethyl 4-methoxy-2-phenylthiazole-5-carboxylate, 4.5 nM for icilin-induced Ca2+ efflux, and 5.5 nM for cold-stimulated Ca2+ efflux.
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| ln Vitro |
In vitro studies demonstrate that TRPM8 antagonist 3 is a potent blocker of TRPM8 with an IC50 of 11 nM. The compound shows inhibitory activity against human TRPM8 receptors expressed in HEK293 cells with IC50 values of 11.0 nM for agonist-induced Ca2+ efflux, 4.5 nM for icilin-induced Ca2+ efflux, and 5.5 nM for cold-stimulated Ca2+ efflux. It exhibits moderate apparent permeability in human corneal epithelial cells at 0.1% concentration. The compound has high solubility at pH 7.4 measured at 9,700,000 nM. In a metabolic stability assay using human liver S9 fraction, it has a half-life of 0.8833 hours. The compound also displays a pKa value of 9.3 and a logD of 0.77 at pH 7.4.
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| ln Vivo |
In vivo studies of TRPM8 antagonist 3 are limited in publicly available literature, as the compound is primarily characterized through in vitro assays. Given its potent TRPM8 antagonism and role in thermosensory pathways, the compound may have potential for in vivo investigations of cold-induced pain, sensory disorders, and thermoregulation. TRPM8 antagonists have been shown to modulate body temperature and pain responses in animal models. However, specific in vivo efficacy, pharmacokinetic, and pharmacodynamic data for this particular compound have not been extensively reported in the available sources. Further animal studies are needed to establish its in vivo activity profile.
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| Enzyme Assay |
For TRPM8 receptor binding and functional assays, HEK293 cells expressing human TRPM8 receptors are cultured and seeded in assay plates. Cells are loaded with calcium-sensitive fluorescent dyes (e.g., Fluo-4 or Fura-2) and incubated with varying concentrations of TRPM8 antagonist 3. TRPM8 activation is induced by agonists such as icilin, menthol, or cold stimulation (typically 10-25°C). Calcium flux is measured using a fluorescence plate reader. IC50 values are calculated from dose-response curves by measuring the reduction in agonist-induced Ca2+ efflux. Non-specific signals are determined using vehicle controls. Assays are performed in replicate wells with appropriate positive controls (e.g., known TRPM8 antagonists).
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| Cell Assay |
For in vitro cellular assays of TRPM8 antagonist 3, HEK293 cells expressing human TRPM8 receptors are cultured in DMEM supplemented with 10% FBS and appropriate selection antibiotics under standard conditions (37°C, 5% CO2). Cells are seeded in 96-well or 384-well plates at appropriate density and allowed to adhere overnight. The compound is dissolved in DMSO and diluted in assay buffer to desired concentrations (typically nM range). Cells are loaded with calcium indicator dye for 30-60 minutes at 37°C. After dye loading, cells are washed and test compound is added. TRPM8 activation is induced by icilin, menthol, or cold stimulation. Fluorescence signals are recorded in real-time. IC50 values are determined from concentration-response curves. Each concentration is tested in triplicate with vehicle and positive controls.
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| Animal Protocol |
For in vivo animal studies of TRPM8 antagonist 3, no specific protocols have been published in the available literature. For general in vivo administration of TRPM8 antagonists, compounds are typically formulated in suitable vehicles (e.g., DMSO/PEG300/saline, or CMC-Na suspensions) and administered via oral gavage, intraperitoneal (i.p.) injection, or intravenous (i.v.) injection. Dosing regimens vary by study objective. For pain models, animals are administered compound prior to nociceptive testing. Body temperature may be monitored as TRPM8 is involved in thermoregulation. Blood samples are collected for pharmacokinetic analysis. All procedures must follow institutional animal care and use committee guidelines.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for TRPM8 antagonist 3 are partially reported. The compound has a molecular weight of 292.31, formula C13H12N2O4S, and CAS number 2102179-29-1. It exhibits high solubility at pH 7.4 (9,700,000 nM) and moderate apparent permeability in human corneal epithelial cells at 0.1%. In human liver S9 fraction metabolic stability assays, it has a half-life of 0.8833 hours. The compound has a pKa of 9.3 and a logD of 0.77 at pH 7.4. Storage: powder at -20°C for up to 3 years; in solvent at -80°C for up to 1 year. Solubility: DMSO 50 mg/mL (171.05 mM) with sonication recommended.
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| Toxicity/Toxicokinetics |
According to available safety information, TRPM8 antagonist 3 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, preferably under a fume hood. 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 is not for human use and no clinical toxicity data are available. Specific GHS hazard classifications for this compound have not been detailed in publicly available sources.
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| References | |
| Additional Infomation |
TRPM8 antagonist 3 is a potent and selective antagonist of the TRPM8 channel with an IC50 of 11 nM. The compound is a valuable research tool for studying thermosensory pathways, peripheral nerve function, and TRPM8-mediated mechanisms in sensory disorders. It has demonstrated potent activity against human TRPM8 receptors with IC50 values of 11.0 nM (agonist-induced), 4.5 nM (icilin-induced), and 5.5 nM (cold-stimulated) Ca2+ efflux. The compound shows potential for developing novel analgesics targeting cold-induced pain and discomfort. It is for research use only with no clinical development or regulatory approvals reported.
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| Molecular Formula |
C13H12N2O4S
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| Molecular Weight |
292.310381889343
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| Exact Mass |
292.051
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| CAS # |
2102179-29-1
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| PubChem CID |
137199889
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
370
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1SC(C2=CC=CC=C2O)=NC=1O)(N1CCCO1)=O
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| InChi Key |
BKUQCBLRBYEPFS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H12N2O4S/c16-9-5-2-1-4-8(9)12-14-11(17)10(20-12)13(18)15-6-3-7-19-15/h1-2,4-5,16-17H,3,6-7H2
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| Chemical Name |
[4-hydroxy-2-(2-hydroxyphenyl)-1,3-thiazol-5-yl]-(1,2-oxazolidin-2-yl)methanone
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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: 25 mg/mL (85.53 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4210 mL | 17.1051 mL | 34.2103 mL | |
| 5 mM | 0.6842 mL | 3.4210 mL | 6.8421 mL | |
| 10 mM | 0.3421 mL | 1.7105 mL | 3.4210 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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