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AMG-517

现货
Catalog No.
A1174
TRPV1拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,700.00
现货
5mg
¥ 1,200.00
现货
25mg
¥ 3,800.00
Ship with 10-15 days
100mg
¥ 8,000.00
Ship with 10-15 days

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Background

AMG-517 is an antagonist of TRPV1 channel with IC50 value of 1-2 nM [1].
TRP1, transient receptor potential cation channel subfamily V member 1, is a subfamily of the transient receptor potential protein group and plays an important role in detecting and regulating body temperature or sensing pain. TRPV1 can be activated by diverse stimuli, including several ingredients of the inflammatory soup which leads to a painful, burning sensation. It is reported that TRPV1 channel may play a pivotal role in many diseases like SIRS [1] [2].
AMG-517 is a TRPV1 antagonist. When tested with stable CHO cell lines expressing TRPV1, treated with AMG-517 inhibited the activation of TRPV1 [1].
In C57BL/6 mice with SIRS induced by LPS, pretreatment with AMG-517 (210 µg/kg) markedly decreased the survival rate and increased the risk of mortality [2]. When tested with Trpv1-/- mice, intraperitoneally treated with AMG-517 (256 nmol/kg) inhibited TRPV1 with inducing hyperthermia in a dose-dependent manner [3]. In capsaicin-induced flinch male Sprague-Dawley rats, oral administration of AMG-517 markedly decreased the number of flinches in a dose-dependent manner [1].
References:
[1].Gavva, N.R., et al., Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J Pharmacol Exp Ther, 2007. 323(1): p. 128-37.
[2].Wanner, S.P., et al., Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory. Cell Cycle, 2012. 11(2): p. 343-9.
[3].Garami, A., et al., Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia. J Neurosci, 2010. 30(4): p. 1435-40.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt430.4
Cas No.659730-32-2
FormulaC20H13F3N4O2S
Solubility≥21.5mg/mL in DMSO
Chemical NameN-[4-[6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl]oxy-1,3-benzothiazol-2-yl]acetamide
SDFDownload SDF
Canonical SMILESCC(=O)NC1=NC2=C(C=CC=C2S1)OC3=NC=NC(=C3)C4=CC=C(C=C4)C(F)(F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

CHO细胞

溶解方法

在DMSO中的溶解度大于21.5mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

1-2 nM

应用

AMG 517是一个选择性的人和大鼠TRPV1拮抗剂,对人和大鼠的解离常数分别为4.2和6.2 nM。在体外,AMG 517能够有效地和完全地抑制辣椒素、质子和热激活的TRPV1。在表达TRPV1的CHO细胞中,AMG 517有效地抑制辣椒素、酸和热诱导的Ca2+摄取,IC50为1-2 nM。

临床实验[2]:

临床样本

健康成年人

剂量

口服给药,2、5和10 mg

应用

在健康成年人中,AMG 517抑制TRPV1活性,引发血药浓度依赖的体温过高。AMG 517通过增加产热和尾皮肤血管收缩,导致体温过高,表明在人类中TRPV1可调控代谢产热和血管张力。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Gavva N R, Bannon A W, Hovland D N, et al. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade[J]. Journal of Pharmacology and Experimental Therapeutics, 2007, 323(1): 128-137.

[2]. Gavva N R, Treanor J J S, Garami A, et al. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans[J]. Pain, 2008, 136(1): 202-210.

生物活性

Description AMG-517 is a highly selective antagonist of TRPV1 with IC50 values of 0.76 nM, 0.62 nM and 1.3 nM for capsaicin-, proton- and heat-induced inward currents, respectively.
Targets capsaicin-induced inward currents proton-induced inward currents heat-induced inward currents      
IC50 0.76 nM 0.62 nM 1.3 nM      

质量控制

质量控制和MSDS

批次:

化学结构

AMG-517