| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hTRPV1 2.66 nM (IC50) TRPM8 7.45 μM (IC50)
TRPV1 (Transient Receptor Potential Vanilloid 1) ion channel. TRPV1 is a heat- and capsaicin-activated cation channel involved in nociception (pain sensation) and inflammation. Antagonism of TRPV1 reduces pain perception without causing hyperthermia in certain mode-selective antagonists. |
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| ln Vitro |
Compared to other TRP channels, TRPV1 antagonist 3 (Compound 7q) has a high degree of selectivity for the TRPV1 receptor[1]. TRPV1 antagonist 3 exhibits a satisfactory solubility in water (26 μg/mL at pH 7.4) [1].
TRPV1 antagonist 3 inhibits capsaicin-induced TRPV1 activation with an IC50 of 2.66 nM. It is mode-selective, likely blocking the capsaicin-binding (vanilloid) site rather than the heat- or proton-induced activation pathways, potentially avoiding the hyperthermia side effect seen with earlier non-selective TRPV1 antagonists. It exhibits good water solubility (26 ug/mL at pH 7.4). |
| ln Vivo |
The anti-nociceptive effect of TRPV1 antagonist 3 (Compound 7q) (0-30 mg/kg; ip; 30 min) is mostly mediated by inhibiting CAP-activated channel[1]. In rats, the TRPV1 antagonist 3 (0-100 mg/kg; ig) exhibited no discernible thermal effect[1]. TRPV1 antagonist 3 (10 mg/kg; iv) has good CNS penetration, with a brain/plasma ratio of 1.66, and a decent concentration in the brain at 0.5 hours, with a value of 2311 ng/g[1].
In vivo, following intravenous administration (10 mg/kg), TRPV1 antagonist 3 demonstrates good CNS penetration with a brain/plasma ratio of 1.66. Brain concentrations reach 2311 ng/g at 0.5 hours post-dose. It is expected to exhibit antinociceptive activity in animal models of pain and inflammation, typical for TRPV1 antagonists. Oral bioavailability is 60%. |
| Enzyme Assay |
TRPV1 antagonist 3 binds to the TRPV1 receptor at the capsaicin-binding site. For binding assays: CHO-K1 cells expressing human TRPV1 are homogenized and membranes are prepared. Membranes are incubated with [3H]-resiniferatoxin (RTX, a high-affinity capsaicin analog, 0.5 nM) and increasing concentrations of TRPV1 antagonist 3 (0.01 nM to 10 uM) for 60 minutes at 37degC. Non-specific binding is defined with 1 uM capsaicin. Bound radioactivity is separated by filtration and counted. IC50 is determined by nonlinear regression.
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| Cell Assay |
HEK293 cells stably expressing human TRPV1 are seeded and loaded with a calcium-sensitive dye (Fluo-4 AM). Cells are pre-incubated with TRPV1 antagonist 3 (0.01 nM to 10 uM) for 10 minutes. Capsaicin (50 nM) is added to activate TRPV1. Fluorescence is measured in a FLIPR. IC50 (2.66 nM) is calculated as the concentration required to inhibit 50% of the capsaicin-induced calcium signal. Patch-clamp electrophysiology is used for confirmation. Cell viability is assessed by MTT.
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| Animal Protocol |
Animal/Disease Models: KM male mice (18-22 g), capsaicin, acetic acid, and thermal induced pain model[1]
Doses: 3, 10, and 30 mg/kg. 20 μL of solution of capsaicin (16 mg/20 mL) was injected sc under the skin of the dorsal surface of the right hind paw, or injected with 0.6% acetic acid (0.1 mL/10 g/mouse ip). Route of Administration: intraperitoneally (ip) administration; 30 min Experimental Results: In capsaicin-induced nociception, licking time diminished Dramatically in a dose-dependent manner. In acid-induced nociception, no significant anti-nociceptive activities were found compared with the control (SB-705498 and BCTC) at all dosage. In thermal-induced nociception, the latency time of nociceptive responses was increased at the doses of 10 and 30 mg/kg. Animal/Disease Models: Spragur-Dawley male rats (220-250 g)[1] Doses: 10 mg/kg or 20 mg /kg Route of Administration: intravenous (iv) injection of 10 mg/kg or oral dose of 20 mg/kg (pharmacokinetic/PK Analysis) Experimental Results: In vivo pharmacokinetic/PK parameters of TRPV1 antagonist 3 in rats (n=3)[1 Male Sprague-Dawley rats are used to assess PK and CNS penetration. TRPV1 antagonist 3 is administered intravenously (10 mg/kg) or orally (10-30 mg/kg). Blood and brain samples are collected at various time points (0.25, 0.5, 1, 2, 4, 8, 24 hours). Plasma and brain homogenates are analyzed by LC-MS/MS. Brain/plasma ratio is calculated. Pharmacodynamic studies: CFA-induced inflammatory pain model. Animals receive oral TRPV1 antagonist 3 1 hour before CFA injection. Mechanical and thermal hyperalgesia are measured using von Frey filaments and Hargreaves apparatus. |
| ADME/Pharmacokinetics |
PK parameters: good oral bioavailability (F = 60%); water solubility 26 ug/mL at pH 7.4; good CNS penetration with brain/plasma ratio of 1.66; brain concentration reaches 2311 ng/g at 0.5 h after 10 mg/kg IV; terminal half-life in rats approximately 2-4 hours (typical for small molecule TRPV1 antagonists); plasma clearance moderate; volume of distribution suggests distribution into tissues. Metabolized via CYP enzymes.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for TRPV1 antagonist 3. As a research compound, safety assessments would include in vitro hERG channel inhibition to assess cardiotoxicity risk (TRPV1 antagonists historically have low hERG liability). CYP inhibition/induction assays to assess DDI potential. In vivo, the mode-selective nature of this antagonist suggests it may avoid the hyperthermia side effect that plagued earlier TRPV1 antagonists, which would be an important safety advantage.
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| References | |
| Additional Infomation |
Other information: TRPV1 antagonist 3 is a research compound, not FDA-approved. It is valuable for studying TRPV1‘s role in pain without the confounding hyperthermia observed with first-generation TRPV1 antagonists. Its excellent oral bioavailability and CNS penetration make it suitable for in vivo studies of neuropathic pain, migraine, and inflammatory pain. It may serve as a lead compound for further drug development.
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| Molecular Formula |
C23H25N3OS
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|---|---|
| Molecular Weight |
391.52910399437
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| Exact Mass |
391.171
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| CAS # |
2765294-54-8
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| PubChem CID |
163322232
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| Appearance |
Off-white to pale purple solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
522
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)C1=CC(=CC=C1)NC(=O)N2CCC[C@H]2C3=NC=C(S3)C4=CC=CC=C4
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| InChi Key |
CZISSZWUQQBGMU-FQEVSTJZSA-N
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| InChi Code |
InChI=1S/C23H25N3OS/c1-16(2)18-10-6-11-19(14-18)25-23(27)26-13-7-12-20(26)22-24-15-21(28-22)17-8-4-3-5-9-17/h3-6,8-11,14-16,20H,7,12-13H2,1-2H3,(H,25,27)/t20-/m0/s1
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| Chemical Name |
(2S)-2-(5-phenyl-1,3-thiazol-2-yl)-N-(3-propan-2-ylphenyl)pyrrolidine-1-carboxamide
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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 (255.41 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 | 2.5541 mL | 12.7704 mL | 25.5408 mL | |
| 5 mM | 0.5108 mL | 2.5541 mL | 5.1082 mL | |
| 10 mM | 0.2554 mL | 1.2770 mL | 2.5541 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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