| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
TC-I 2014 targets the transient receptor potential melastatin 8 (TRPM8) channel, a cold- and menthol-activated ion channel involved in thermosensation and pain perception. By antagonizing TRPM8, TC-I 2014 blocks cold-induced and menthol-induced calcium influx through the channel. The compound exhibits antiallodynic properties in pain models and is used to study TRPM8 function in pain and sensory disorders.
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| ln Vitro |
With IC50 values of 0.413 and 1 nM, respectively, TC-I 2014 (compound 5) may effectively suppress cold-induced TRPM8 current in HEK293 cells that are stable TRPM8-expressing canines or humans [1].
In vitro, TC-I 2014 is a potent TRPM8 antagonist with IC50 values of 0.8 nM for canine, 3.0 nM for human, and 4.4 nM for rat channels. It is orally active and exhibits antiallodynic properties in pain models. The compound's activity is assessed by measuring calcium flux in cells expressing TRPM8 channels. |
| ln Vivo |
When given orally, TC-I 2014 (10 mg/kg) totally eliminates WDS brought on by cillin[1].
In vivo, TC-I 2014 exhibits antiallodynic properties in pain models. By blocking TRPM8 channels, the compound reduces cold-induced pain and allodynia. It has potential applications in the study and treatment of pain conditions where TRPM8 plays a role, such as neuropathic pain, migraine, and cold hyperalgesia. |
| Enzyme Assay |
In vitro receptor binding/functional assays for TC-I 2014 measure its inhibition of TRPM8-mediated calcium influx. Cells expressing canine, human, or rat TRPM8 channels are treated with serial dilutions of the compound, and calcium flux is measured using fluorescent calcium indicators upon TRPM8 activation by cold or menthol. IC50 values of 0.8 nM, 3.0 nM, and 4.4 nM are determined for canine, human, and rat channels, respectively.
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| Cell Assay |
In vitro cell-based assays for TC-I 2014 use cells expressing TRPM8 channels. Cells are treated with serial dilutions of the compound, and TRPM8-mediated calcium influx is measured using fluorescent calcium indicators. The IC50 for inhibition of TRPM8 activation is calculated from dose-response curves. Cell viability is assessed in parallel.
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| Animal Protocol |
Animal/Disease Models: TC-I 2014 (10 mg/kg, taken orally once) completely prevents cillin-induced WDS[1].
Doses: 3, 5.6, 10 mg/kg. Doses: Take once orally. Experimental Results: 3, 5.6, and 10 mg/kg administered 2 hrs (hrs (hours)) before cillin challenge produced greater than 90% inhibition. In vivo animal models for TC-I 2014 include models of pain such as cold allodynia, neuropathic pain, and inflammatory pain. The compound is administered orally, and its effects on pain behavior, allodynia, and hyperalgesia are evaluated. Pharmacodynamic studies measure TRPM8 antagonism and pain relief in response to compound treatment. |
| ADME/Pharmacokinetics |
TC-I 2014 has a molecular formula of C23H19F6N3O and a molecular weight of 467.41 g/mol. It is soluble in DMSO at 46.74 mg/mL and is stored as a powder at -20°C for up to 3 years. The compound has a purity of ≥98%. It is also known as compound 5.
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| Toxicity/Toxicokinetics |
The toxicity profile of TC-I 2014 is characterized in preclinical safety studies. As a TRPM8 antagonist, the compound may affect thermosensation and pain perception. The compound is for research use only and is not approved for clinical use. Appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
TC-I 2014 is a potent and orally active TRPM8 antagonist with IC50 values of 0.8 nM, 3.0 nM, and 4.4 nM for canine, human, and rat channels, respectively. It exhibits antiallodynic properties in pain models. TC-I 2014 is a benzimidazole-containing compound and is also known as compound 5. It is intended for laboratory research use only.
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| Molecular Formula |
C23H19F6N3O
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|---|---|
| Molecular Weight |
467.406886339188
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| Exact Mass |
467.143
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| Elemental Analysis |
C, 59.10; H, 4.10; F, 24.39; N, 8.99; O, 3.42
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| CAS # |
1221349-53-6
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| PubChem CID |
135883253
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| Appearance |
White to off-white solid powder
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
33
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| Complexity |
748
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC2(CC1)CC(=NO2)C3=NC4=C(C=C(C=C4N3)C5=CC=CC=C5C(F)(F)F)C(F)(F)F
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| InChi Key |
VSMFCZZEKTVDHM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H19F6N3O/c24-22(25,26)15-7-3-2-6-14(15)13-10-16(23(27,28)29)19-17(11-13)30-20(31-19)18-12-21(33-32-18)8-4-1-5-9-21/h2-3,6-7,10-11H,1,4-5,8-9,12H2,(H,30,31)
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| Chemical Name |
3-[4-(trifluoromethyl)-6-[2-(trifluoromethyl)phenyl]-1H-benzimidazol-2-yl]-1-oxa-2-azaspiro[4.5]dec-2-ene
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| Synonyms |
TCI 2014; TC I 2014; TC-I 2014
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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 : ~250 mg/mL (~534.86 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 | 2.1394 mL | 10.6972 mL | 21.3945 mL | |
| 5 mM | 0.4279 mL | 2.1394 mL | 4.2789 mL | |
| 10 mM | 0.2139 mL | 1.0697 mL | 2.1394 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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