AMG 9810
(Synonyms: (2E)-N-(2,3-二氢-1,4-苯并二噁英-6-基)-3-[4-(1,1-二甲基乙基)苯基]-2-丙酰胺) 目录号 : GC11926
AMG 9810是一种高选择性和竞争性TRPV1拮抗剂（人：IC50 = 24.5nM；小鼠：IC50 = 85.6nM）。
Cas No.:545395-94-6
Sample solution is provided at 25 µL, 10mM.
AMG 9810 is a highly selective and competitive TRPV1 antagonist (human: IC50 = 24.5nM; mouse: IC50 = 85.6nM) [1]. AMG 9810 blocks TRPV1 channels activated by capsaicin, acidic conditions, heat, and endogenous ligands such as anandamide, inhibiting ion influx into cells and thereby attenuating the transmission of pain and heat-sensitive signals [2-3]. AMG 9810 exhibits anti-hyperalgesia, anti-inflammatory, and analgesic effects [4].
In HEKn cells, AMG 9810 (0–5μM; 24-72h) was cytotoxic to these cells at the higher concentrations tested and when exposed for longer in culture [5]. In T84 cells, AMG 9810 (100nM; 30min) can block the increase in [Ca2+]i induced by capsaicin and resiniferatoxin [6]. In chinese hamster ovary (CHO) cell, AMG 9810 (3-1000nM; 10min) penetrates faster than capsaicin and is more potent than capsaicin [7].
In Male Wister rats, AMG 9810 (30mg/kg; ip; single injection) injection can induce mild hyperthermia in rats immediately [8]. In C57BL6 mice, AMG 9810 (1nmol; intrathecal injections; single injection) completely blocked NADA-induced allergy 15 and 60 minutes after injection [9].
References:
[1]. Gavva N R, Tamir R, Qu Y, et al. AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2, 3-dihydrobenzo [b][1, 4] dioxin-6-yl) acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties[J]. The journal of pharmacology and experimental therapeutics, 2005, 313(1): 474-484.
[2]. Gomtsyan A. Aryl‐Urea Class and Related TRPV1 Antagonists[J]. Vanilloid Receptor TRPV1 in Drug Discovery: Targeting Pain and Other Pathological Disorders, 2010: 293-310.
[3]. Hakimizadeh E, Oryan S, Shamsizadeh A, et al. Endocannabinoid system and TRPV1 receptors in the dorsal hippocampus of the rats modulate anxiety-like behaviors[J]. Iranian Journal of Basic Medical Sciences, 2012, 15(3): 795.
[4]. Gomtsyan A. Aryl‐Urea Class and Related TRPV1 Antagonists[J]. Vanilloid Receptor TRPV1 in Drug Discovery: Targeting Pain and Other Pathological Disorders, 2010: 293-310.
[5]. Park M, Naidoo A A, Burns A, et al. Do TRPV1 antagonists increase the risk for skin tumourigenesis? A collaborative in vitro and in vivo assessment[J]. Cell Biology and Toxicology, 2018, 34(2): 143-162.
[6]. Bouyer P G, Tang X, Weber C R, et al. Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2013, 304(2): G142-G156.
[7]. Pearce L V, Ann J, Blumberg P M, et al. Combination of a Rapidly Penetrating Agonist and a Slowly Penetrating Antagonist Affords Agonist Action of Limited Duration at the Cellular Level[J]. Biomolecules & Therapeutics, 2019, 27(5): 435.
[8]. Tejada de Rink M M, Naumann U, Kollmar R, et al. A Single Injection of N-Oleoyldopamine, an Endogenous Agonist for Transient Receptor Potential Vanilloid-1, Induced Brain Hypothermia, but No Neuroprotective Effects in Experimentally Induced Cerebral Ischemia in Rats[J]. Therapeutic Hypothermia and Temperature Management, 2020, 10(2): 91-101.
[9]. Pitcher M H, Price T J, Entrena J M, et al. Spinal NKCC1 blockade inhibits TRPV1-dependent referred allodynia[J]. Molecular pain, 2007, 3: 1744-8069-3-17.
AMG 9810是一种高选择性和竞争性TRPV1拮抗剂（人：IC50 = 24.5nM；小鼠：IC50 = 85.6nM） [1]。AMG 9810可阻断由辣椒素、酸性环境、高温以及内源性配体（如花生四烯乙醇胺）激活的TRPV1通道，抑制离子内流进入细胞，从而减弱痛觉和热敏信号的传递 [2-3]。AMG 9810具有抗痛觉过敏、抗炎和镇痛作用 [4]。
在HEKn细胞中，AMG 9810（0-5μM；24-72h）在较高测试浓度下以及在培养条件下暴露时间较长时均对这些细胞表现出细胞毒性 [5]。在T84细胞中，AMG 9810（100nM；30min）可以阻断辣椒素和树脂毒素引起的[Ca2+]i升高 [6]。在中国仓鼠卵巢（CHO）细胞中，AMG 9810（3-1000nM；10min）的渗透速度比辣椒素更快，作用也比辣椒素更强 [7]。
在雄性Wister大鼠中，AMG 9810（30mg/kg；ip；单次注射）注射后可立即引起大鼠轻度高热 [8]。在C57BL6小鼠中，AMG 9810（1nmol；鞘内注射；单次注射）在注射后15和60分钟完全阻断了NADA诱发的过敏反应 [9]。
| Cell experiment [1]: | |
Cell lines | HEKn cells |
Preparation Method | HEKn cells were plated in 24-well plates (2 × 104 cells per well in 1mL of culture medium) or in 6-well plates (9.6 × 104 cells per well in 2mL of culture medium) and incubated overnight at 37℃. The culture medium was replaced with or without various concentrations of SB-705498 and AMG 9810, at a final concentration of 0.1% v/v DMSO, and the MTT assay was performed after 24, 48, and 72 hours of incubation. |
Reaction Conditions | 0–5μM; 24-72h |
Applications | AMG 9810 was cytotoxic to these cells at the higher concentrations tested and when exposed for longer in culture. |
| Animal experiment [2]: | |
Animal models | Male Wister rats |
Preparation Method | Animals (n = 12) were randomly allocated before surgery to vehicle, OLDA (30mg/kg), or AMG 9810 (30mg/kg) treatment groups. Dummy cannulas were removed and the thermocouple wire sensors were inserted in the guide cannula. Animals were then left undisturbed in the telemetry cages for 60 minutes to measure baseline temperatures and gross activities. The injection solutions (1mL DMSO, 15mg OLDA in 1mL DMSO, and 15mg AMG 9810 in 1mL DMSO) were prepared for administration in a blinded manner. |
Dosage form | 30mg/kg; ip; single injection |
Applications | AMG 9810 injection can induce mild hyperthermia in rats immediately. |
References: | |
| Cas No. | 545395-94-6 | SDF | |
| 别名 | (2E)-N-(2,3-二氢-1,4-苯并二噁英-6-基)-3-[4-(1,1-二甲基乙基)苯基]-2-丙酰胺 | ||
| 化学名 | (Z)-3-(4-(tert-butyl)phenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide | ||
| Canonical SMILES | O=C(/C=C\C1=CC=C(C=C1)C(C)(C)C)NC2=CC=C3OCCOC3=C2 | ||
| 分子式 | C21H23NO3 | 分子量 | 337.42 |
| 溶解度 | ≥ 33.7mg/mL in DMSO | 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 | 2.9637 mL | 14.8183 mL | 29.6367 mL |
| 5 mM | 0.5927 mL | 2.9637 mL | 5.9273 mL |
| 10 mM | 0.2964 mL | 1.4818 mL | 2.9637 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)
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