| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
TRPV1 (Transient Receptor Potential Vanilloid-1).
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|---|---|
| ln Vitro |
A-1165442 displays effective competitive antagonism (IC50=9 nM) against capsaicin-activated recombinant human TRPV1 and does not entirely block acid-evoked responses (62% block at 30 μM). A-1165442 exhibits exceptional Selectivity (>100 times)/3. A-1165442 demonstrated low cross-reactivity when assessed (10 μM) in a large screening panel of cell surface receptors, ion channels and enzymes (n=74, CEREP) [1].
A-1165442 is a potent, competitive antagonist of recombinant human TRPV1 with an IC50 of 9 nM when activated by capsaicin. It achieves a 62% block at 30 uM in acid-evoked responses, indicating incomplete blockade. It is a second-generation TRPV1 antagonist with a temperature-neutral profile. |
| ln Vivo |
A-1165442 has superior pharmacokinetic characteristics, good pharmacological selectivity, and encouraging efficacy against rodent osteoarthritis pain. Rats with an ED50 of 9.5 μmol/kg, or 420 ng/mL (970 nM) of capsaicin-induced nociceptive behavior are prevented from acting when A-1165442 is administered orally. With an ED50 of 35 μmol/kg determined an hour after administration, a single dose of A-1165442 produced a strong effect on grip strength. A-1165442 was more potent with repeated treatment in comparison to its acute analgesic efficacy. A-1165442 did not significantly alter the core body temperature of aware rats, and conscious dogs also maintained this temperature-neutral profile [1].
A-1165442 has shown significant analgesic efficacy in rodent models of osteoarthritis pain. It reduces pain without causing hyperthermia, which is a common side effect of first-generation TRPV1 antagonists. |
| Enzyme Assay |
TRPV1 receptor binding assays are performed using membrane preparations from cells expressing human TRPV1. Radiolabeled ligand (e.g., [3H]-resiniferatoxin) displacement assays determine the compound's affinity. Functional assays measure capsaicin- or acid-induced calcium influx in TRPV1-expressing cells.
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| Cell Assay |
Cells expressing human TRPV1 (e.g., HEK-293 or CHO cells) are treated with A-1165442 and stimulated with capsaicin or acid (pH 5.5). Calcium influx is measured using fluorescent calcium indicators (e.g., Fluo-4). IC50 values for inhibition of capsaicin- and acid-evoked responses are determined.
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| Animal Protocol |
Rodent models of pain (e.g., osteoarthritis pain model, inflammatory pain model) are used to assess analgesic efficacy. Animals are treated orally with A-1165442 and pain responses (e.g., mechanical allodynia, thermal hyperalgesia) are measured. Body temperature is monitored to confirm the temperature-neutral profile.
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| ADME/Pharmacokinetics |
A-1165442 is orally bioavailable. The compound has good pharmacokinetic properties suitable for oral administration. Specific parameters (half-life, clearance, volume of distribution) have not been reported but are consistent with drug-like properties.
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| Toxicity/Toxicokinetics |
No significant toxicity reported at therapeutic doses. The temperature-neutral profile suggests reduced risk of hyperthermia compared to first-generation TRPV1 antagonists. Standard safety pharmacology studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
A-1165442 is a second-generation TRPV1 antagonist developed for the treatment of pain. It has shown good analgesic efficacy in preclinical models with a favorable temperature-neutral profile. The compound has not been approved for clinical use but represents an important research tool for studying TRPV1-mediated pain pathways.
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| Molecular Formula |
C22H20CLF2N3O2
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|---|---|
| Molecular Weight |
431.862911224365
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| Exact Mass |
431.121
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| CAS # |
1221443-94-2
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| PubChem CID |
46191567
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
574.4±50.0 °C at 760 mmHg
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| Flash Point |
301.2±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.635
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| LogP |
4.36
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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 |
4
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| Heavy Atom Count |
30
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| Complexity |
609
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC2=C(C=CC=C2NC(=O)N[C@@H]3CC(OC4=C3C=CC(=C4)Cl)(CF)CF)C=N1
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| InChi Key |
VJJGAJAUECQWSZ-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C22H20ClF2N3O2/c1-13-7-17-14(10-26-13)3-2-4-18(17)27-21(29)28-19-9-22(11-24,12-25)30-20-8-15(23)5-6-16(19)20/h2-8,10,19H,9,11-12H2,1H3,(H2,27,28,29)/t19-/m1/s1
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| Chemical Name |
1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydrochromen-4-yl]-3-(3-methylisoquinolin-5-yl)urea
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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 (~231.56 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 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 25.0 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: ≥ 2.5 mg/mL (5.79 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 25.0 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 | 2.3156 mL | 11.5778 mL | 23.1557 mL | |
| 5 mM | 0.4631 mL | 2.3156 mL | 4.6311 mL | |
| 10 mM | 0.2316 mL | 1.1578 mL | 2.3156 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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