AMG 9810

Names

[ Name ]:
AMG 9810

[Synonym ]:
(2E)-N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(2-methyl-2-propanyl)phenyl]acrylamide
(2E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-enamide
2-Propenamide, N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[4-(1,1-dimethylethyl)phenyl]-, (2E)-
(2E)-3-(4-tert-Butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)acrylamide
amg 9810
AMG9810

Biological Activity

[Description]:

AMG9810 is a selective and competitive vanilloid receptor 1 (TRPV1) antagonist with IC50 values of 24.5 and 85.6 nM for human and rat TRPV1, repectively.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Neurological Disease

[Target]

IC50: 24.5 nM (human TRPV1), 85.6 nM (rat TRPV1)[1]

[In Vitro]

AMG9810 is a competitive antagonist of capsaicin activation (IC50 value for human TRPV1, 24.5±15.7 nM; rat TRPV1, 85.6±39.4 nM) and blocks all known modes of TRPV1 activation, including protons (IC50 value for rat TRPV1, 294±192 nM; human TRPV1, 92.7±72.8 nM), heat (IC50 value for rat TRPV1, 21±17 nM; human TRPV1, 15.8±10.8 nM), and endogenous ligands, such as anandamide, N-arachidonyl dopamine, and oleoyldopamine. AMG9810 blocks capsaicin-evoked depolarization and calcitonin gene-related peptide release in cultures of rat dorsal root ganglion primary neurons. AMG9810 inhibits capsaicin-, proton-, heat-, and endogenous ligand-induced uptake of 45Ca2+ into TRPV1-expressing cells[1].

[In Vivo]

AMG9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and it reverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant. At effective doses, AMG9810 does not show any significant effects on motor function. AMG9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain[1]. AMG9810, promotes mouse skin tumor development. The topical application of AMG9810 results in a significant increase in the expression level of the epidermal growth factor receptor (EGFR) and its downstream Akt/mammalian target of rapamycin (mTOR)-signaling pathway[2].

[Kinase Assay]

Cultured adult rat dorsal root ganglia neurons in 96-well plates are washed twice with release buffer to initiate the 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 room temperature. The extracellular medium is collected and the CGRP content is determined using a commercially kit[1].

[Cell Assay]

To assess cyotoxicity of AMG9810, N/TERT1 cells are treated with different concentrations of AMG9810 (0.25, 0.5, 1, 5 μM) and cultured for various periods of time (24, 48, 72 h). The CellTiter 96 AQueous One Solution is added to each well and then cells are kept in a 37°C, 5% CO2 incubator for 1 h. Absorbance is then measured at 492 and 690 nm with a plate reader[2].

[Animal admin]

Rats: AMG9810 is dissolved in DMSO. Rats are acclimated for 30 to 45 min in a 30×30×30-cm Plexiglas chambers before the intraperitoneal injection of either vehicle (DMSO) or AMG 9810. Injections are made over a 5-s period in the lower right ventral quadrant of the abdomen either 15, 30, or 60 min before intraocular application of capsaicin. Intraocular application of capsaicin (3 μg/20 μL in 10% ethanol/PBS) or vehicle (20 μL in 10% ethanol/PBS) is done with a pipette, and the number of front paw eye wipes is counted over a 5-min period in 1-min intervals [1].

[References]

[1]. Gavva NR, et al. AMG9810 [(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 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. Carcinogenesis. 2011 May;32(5):779-85.

[Related Small Molecules]

capsaicin | Capsazepine | EIPA | Diphenyleneiodonium chloride | HC-030031 | SKF-96365 | HC 067047 | GSK-1016790A | SAR7334 | PF-4840154 | RN-1734 | AMG-517 | SB-366791 | IcilinAG-3-5 | ML204

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
512.5±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₁H₂₃NO₃

[ Molecular Weight ]:
337.412

[ Flash Point ]:
263.8±30.1 °C

[ Exact Mass ]:
337.167786

[ PSA ]:
47.56000

[ LogP ]:
5.47

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.618

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H319-H413

[ Precautionary Statements ]:
P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

[ RIDADR ]:
NONH for all modes of transport

Articles

Spinal NKCC1 blockade inhibits TRPV1-dependent referred allodynia.

Mol. Pain 3 , 17, (2007)

The Na+, K+, 2Cl- type I cotransporter (NKCC1) and TRPV1 receptors, at the level of the dorsal horn, have been implicated in mediating allodynia in response to an inflammatory insult. The NKCC1 cotran...

Endocannabinoid System and TRPV1 Receptors in the Dorsal Hippocampus of the Rats Modulate Anxiety-like Behaviors.

Iran. J. Basic Med. Sci. 15 , 795-802, (2013)

Fatty acid is amide hydrolase which reduce endogenous anandamide. Transient receptor potential vanilloid-1 (TRPV1) channels have been reported to have a role in the modulation of anxiety-like behavior...