1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAMG9810Cat. No.: HY-101736CAS No.: 545395-94-6分式: CHNO分量: 337.41作靶點: TRP Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 33 m

2、g/mL (97.80 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.9638 mL 14.8188 mL 29.6375 mL5 mM 0.5928 mL 2.9638 mL 5.9275 mL10 mM 0.2964 mL 1.4819 mL 2.9638 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為

3、保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.41 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.41 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 9

4、0% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (7.41 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AMG9810選擇性和競爭性的草素受體1 (TRPV1) 拮抗劑，對類和TRPV1的IC50值分別為24.5 和 85.6nM。IC50 & Target IC50: 24.5 nM (human TRPV1), 85.6 nM (rat TRPV1) 1體外研究 AMG9810 is a competitive antagonist o

5、f capsaicin activation (IC50 value for human TRPV1, 24.515.7 nM;rat TRPV1, 85.639.4 nM) and blocks all known modes of TRPV1 activation, including protons (IC50 valuefor rat TRPV1, 294192 nM; human TRPV1, 92.772.8 nM), heat (IC50 value for rat TRPV1, 2117 nM;human TRPV1, 15.810.8 nM), and endogenous

6、ligands, such as anandamide, N-arachidonyl dopamine,and oleoyldopamine. AMG9810 blocks capsaicin-evoked depolarization and calcitonin gene-related peptiderelease in cultures of rat dorsal root ganglion primary neurons. AMG9810 inhibits capsaicin-, proton-, heat-,and endogenous ligand-induced uptake

7、of 45Ca2+ into TRPV1-expressing cells 1.體內(nèi)研究 AMG9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and itreverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantarinjection of complete Freunds adjuvant. At effective dose

8、s, AMG9810 does not show any significant effectson motor function. AMG9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-inducedeye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain 1. AMG9810,promotes mouse skin tumor development. The topical app

9、lication of AMG9810 results in a significantincrease in the expression level of the epidermal growth factor receptor (EGFR) and its downstreamAkt/mammalian target of rapamycin (mTOR)-signaling pathway 2.PROTOCOLKinase Assay 1 Cultured adult rat dorsal root ganglia neurons in 96-well plates are washe

10、d twice with release buffer to initiatethe assay. CGRP release is induced by incubation of neurons with capsaicin for 10 min at room temperature.The cultures are preincubated with increasing concentrations of capsazepine or AMG9810 for 15 min,followed by 300 nM capsaicin activation for 10 min at roo

11、m temperature. The extracellular medium iscollected and the CGRP content is determined using a commercially kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 To assess cyotoxicity of AMG9810, N/TERT1 cells are treated with different con

12、centrations of AMG9810(0.25, 0.5, 1, 5 M) and cultured for various periods of time (24, 48, 72 h). The CellTiter 96 AQueous OneSolution is added to each well and then cells are kept in a 37C, 5% CO2 incubator for 1 h. Absorbance isthen measured at 492 and 690 nm with a plate reader 2.MCE has not ind

13、ependently confirmed the accuracy of these methods. They are for reference only.Animal Rats: AMG9810 is dissolved in DMSO. Rats are acclimated for 30 to 45 min in a 303030-cm Plexiglas2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 1 chambers before the intraperitoneal injection of e

14、ither vehicle (DMSO) or AMG 9810. Injections are madeover a 5-s period in the lower right ventral quadrant of the abdomen either 15, 30, or 60 min beforeintraocular application of capsaicin. Intraocular application of capsaicin (3 g/20 L in 10% ethanol/PBS) orvehicle (20 L in 10% ethanol/PBS) is don

15、e with a pipette, and the number of front paw eye wipes is countedover a 5-min period in 1-min intervals 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Gavva NR, et al. AMG9810 (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzob1,4 dioxin-6-yl)acrylamide, a novel vanilloid receptor 1(TRPV1) antagonist with antihyperalgesic properties. J Pharmacol Exp Ther. 2005 Apr;313(1):474-84.2. Li S, et al. TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling.