A-1165442 |
| カタログ番号GC30837 |
A-1165442 は、ヒト TRPV1 に対して 9 nM の IC50 を持つ、強力で競合的で経口的に利用可能な TRPV1 アンタゴニストです。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1221443-94-2
Sample solution is provided at 25 µL, 10mM.
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A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC50 of 9 nM for human TRPV1.
A-1165442 displays potent, competitive antagonism at recombinant human TRPV1 activated by capsaicin (IC50=9 nM) and incomplete blockade of acid-evoked response (62% block at 30 μM). A-1165442 possesses excellent selectivity (>100-fold) versus other members of the TRP family (TRPA1, TRPM8, TRPV2, TRPV3) and other receptors expressed in peripheral sensory neurons including P2X2/3, Cav2.2, Nav channels, and KCNQ2/3. A-1165442 shows minimal cross-reactivity upon evaluation (10 μM) in a broad screening panel (n=74, CEREP) of cell-surface receptors, ion channels, and enzymes[1].
A-1165442 exhibits excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents. Oral administration of A-1165442 prevents capsaicin-induced nocifensive behaviors in rats, with an ED50 of 9.5 μmol/kg corresponding to plasma concentration of 420 ng/mL (970 nM). A single dose of A-1165442 produces a robust effect on grip force, with an ED50 of 35 μmol/kg measured 1 h postdosing. Repeated dosing of A-1165442 results in an increase in potency relative to acute analgesic efficacy. No significant changes in core body temperature is observed in conscious rats dosed with A-1165442 and this temperature-neutral profile is maintained in conscious dogs[1].
[1]. Voight EA, et al. Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy. J Med Chem. 2014 Sep 11;57(17):7412-24.
Animal experiment: | Dogs: Male beagle dogs are instrumented with telemetry transmitters capable of monitoring core body temperature and then allowed to recover. Dosing is initiated at time zero, with dogs receiving a single oral dose of vehicle, compound 1 at (30 μmol/kg), or A-1165442 (100 μmol/kg); n=4−6 per group. Measurements are recorded every 5 min for the duration of the study, then averaged to 15 min and 1 h intervals. Temperature signals are transmitted as radio signals by each implanted transmitter to a receiver placed on the cage and interfaced with a desktop personal computer[1]. |
References: [1]. Voight EA, et al. Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy. J Med Chem. 2014 Sep 11;57(17):7412-24. | |
| Cas No. | 1221443-94-2 | SDF | |
| Canonical SMILES | O=C(NC1=CC=CC2=C1C=C(C)N=C2)N[C@H]3C4=CC=C(Cl)C=C4OC(CF)(CF)C3 | ||
| Formula | C22H20ClF2N3O2 | M.Wt | 431.86 |
| 溶解度 | DMSO : ≥ 100 mg/mL (231.56 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3156 mL | 11.5778 mL | 23.1557 mL |
| 5 mM | 463.1 μL | 2.3156 mL | 4.6311 mL |
| 10 mM | 231.6 μL | 1.1578 mL | 2.3156 mL |
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Quality Control & SDS
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- Purity: >99.50%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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