AM-0902
目录号 : GC19025
AM-0902 是一种有效的选择性瞬时受体电位 A1 (TRPA1) 拮抗剂，对 rTRPA1 和 hTRPA1 的 IC50 分别为 71 和 131 nM。
Cas No.:1883711-97-4
Sample solution is provided at 25 µL, 10mM.
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AM-0902 is a potent, selective transient receptor potential A1 (TRPA1) antagonist with IC50s of 71 and 131 nM for rTRPA1 and hTRPA1, respectively.
AM-0902 is a potent, selective antagonist of TRPA1 with IC50s of 71 and 131 nM for rTRPA1 and hTRPA1, respectively. AM-0902 is highly permeable (average Papp=44.5 ucm/s in MDCK cells), an unlikely substrate for P-gp (efflux ratio=1.3 in P-gp overexpressing MDCK cells), and demonstrates good solubility (PBS pH 7.4: 226 uM, SIF: 248 uM). AM-0902 shows good selectivity over other TRP channels, as no activity is observed against human TRPV1 or TRPV4, or rat TRPV1, TRPV3, or TRPM8, at concentrations up to 10 uM. AM-0902 inhibits 45Ca2+ flux upon activation of rat TRPA1 with methylglyoxal with an IC50 of 0.019 uM[1].
AM-0902 is a potent, selective antagonist of TRPA1 in vivo. AM-0902 has moderate terminal elimination half-life (t1/2=0.6 h and 2.8 h for rat (0.5 mg/kg, iv), rat (30 mg/kg, oral)). A dose-dependent reduction of allyl isothiocyanate (AITC)-induced flinching is observed for AM-0902, with a significant reduction in flinching observed postdosing of 10 and 30 mg/kg. The unbound plasma concentrations (Cu) at 1 h for the 1, 3, 10, and 30 mg/kg doses are 0.051±0.024 (n=8), 0.19±0.11 (n=8), 0.58±0.35 (n=8), and 2.2±0.40 (n=8) uM, covering the in vitro rat TRPA1 45Ca2+ IC50 at 0.72, 2.7, 8.2, and 30.3 fold, respectively. A good exposure-response relationship is observed in this target coverage model. An unbound in vivo IC50 of 0.35 uM, which is in good agreement with the in vitro rat TRPA1 45Ca2+ IC50, and unbound in vivo IC90 of 1.7 uM are determined. It is noteworthy that at a dose of 30 mg/kg, AM-0902 engages TRPA1 at concentrations that exceed the in vivo IC90, making it a useful tool for exploration of in vivo models of acute pain[1].
References:
[1]. Schenkel LB, et al. Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1)Antagonists Demonstrating Potent in Vivo Activity. J Med Chem. 2016 Mar 24;59(6):2794-809.
Cell experiment: | MDCK cells are generated and maintained for the TRPA1 calcium flux assays. On the day of assay, culture media is removed and cells are incubated for 10 min at room temperature (RT) with 50 μL of AM-0902 (compound 27) in AM-0902 dilution buffer [HBSS containing 1 mM HEPES+0.1 mg/mL BSA] at final concentrations (2.0 nM to 40 μM, 1:3 ratio), followed by another 3 min incubation at RT. The reaction mixture is aspirated, and cells are washed three times with phosphate buffer saline (PBS) containing 0.1 mg/mL BSA. Radioactivity is measured using a TopCount microplate scintillation counter. The activation of TRPA1 is measured by the cellular uptake of radioactive calcium[1]. |
Animal experiment: | Rats[1]Rats are dosed orally with either vehicle (2% HPMC/1% Tween-80) or AM-0902 at 1, 3, 10, or 30 mg/kg. After 1 h, one left ventral hind paw is injected with the TRPA1 agonist AITC (0.1%). AM-0902 is also given by an intravenous (IV) injection to rats (0.5 mg/kg)[1]. |
References: [1]. Schenkel LB, et al. Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1)Antagonists Demonstrating Potent in Vivo Activity. J Med Chem. 2016 Mar 24;59(6):2794-809. | |
| Cas No. | 1883711-97-4 | SDF | |
| Canonical SMILES | O=C1N(CC2=NC(CCC3=CC=C(Cl)C=C3)=NO2)C=NC4=C1N(C)C=N4 | ||
| 分子式 | C17H15ClN6O2 | 分子量 | 370.79 |
| 溶解度 | DMSO : 150 mg/mL (404.54 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 | 2.6969 mL | 13.4847 mL | 26.9694 mL |
| 5 mM | 0.5394 mL | 2.6969 mL | 5.3939 mL |
| 10 mM | 0.2697 mL | 1.3485 mL | 2.6969 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。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet