A-1165442
目录号 : GC30837
A-1165442是有效，竞争性，有口服活性的TRPV1拮抗剂，对人TRPV1的IC50值为9nM。
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 | ||
| 分子式 | C22H20ClF2N3O2 | 分子量 | 431.86 |
| 溶解度 | DMSO : ≥ 100 mg/mL (231.56 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet