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Purity: ≥98%
AMG9810 (AMG-9810) is a nove, potent, selective and competitive antagonist of vanilloid receptor 1 (TRPV1) with cancer-promoting effects. It inhibits TRPV1 with IC50 values of 24.5 and 85.6 nM for human and rat TRPV1, repectively. AMG9810 promotes mouse skin tumor development. The topical application of AMG9810 resulted 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. This increase was not only observed in AMG9810-treated tumor tissue but was also found in skin tissue treated with AMG9810. In telomerase-immortalized primary human keratinocytes, AMG9810 promoted proliferation that was mediated through the EGFR/Akt/mTOR-signaling pathway. In summary, our data suggest that the TRPV1 antagonist, AMG9810, promotes mouse skin tumorigenesis mediated through EGFR/Akt/mTOR signaling. Thus, the application of this compound for pain relief might increase the risk of skin cancer.
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| ln Vitro |
In cultures of rat dorsal root ganglion primary neurons, AMG9810 blocks capsaicin-evoked depolarization and calcitonin gene-related peptide release. It also inhibits capsaicin-, proton-, heat-, and endogenous ligand-induced uptake of 45Ca2+ into TRPV1-expressing cells. 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). It blocks all known modes of TRPV1 activation, including protons (IC50 value for rat TRPV1, 294±192 nM).
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| ln Vivo |
In a model of inflammatory pain caused by intraplantar injection of complete Freund's adjuvant, AMG9810 reverses thermal and mechanical hyperalgesia and is effective in reducing capsaicin-induced eye wiping in a dose-dependent manner. AMG9810 has no discernible impact on motor function at effective levels. In an animal model of inflammatory pain, AMG9810 is the first cinnamide TRPV1 antagonist that has been shown to inhibit capsaicin-induced eye wiping behavior and reverse hyperalgesia[1]. AMG9810 stimulates the growth of cutaneous tumors in mice. The epidermal growth factor receptor (EGFR) and its downstream Akt/mammalian target of rapamycin (mTOR)-signaling pathway are significantly upregulated upon topical administration of AMG9810[2].
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| 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 |
| Molecular Formula |
C21H23NO3
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|---|---|
| Molecular Weight |
337.4122
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| CAS # |
545395-94-6
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| SMILES |
CC(C)(C)c1ccc(cc1)/C=C/C(=O)Nc2ccc3c(c2)OCCO3
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| InChi Key |
GZTFUVZVLYUPRG-IZZDOVSWSA-N
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| InChi Code |
InChI=1S/C21H23NO3/c1-21(2,3)16-7-4-15(5-8-16)6-11-20(23)22-17-9-10-18-19(14-17)25-13-12-24-18/h4-11,14H,12-13H2,1-3H3,(H,22,23)/b11-6+
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| Chemical Name |
3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
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| Synonyms |
AMG9810; AMG-9810; AMG 9810.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 33 mg/mL (~97.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9638 mL | 14.8188 mL | 29.6375 mL | |
| 5 mM | 0.5928 mL | 2.9638 mL | 5.9275 mL | |
| 10 mM | 0.2964 mL | 1.4819 mL | 2.9638 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 AMG9810 promotes mouse skin tumorigenesis.Carcinogenesis.2011 May;32(5):779-85 |
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 The EGFR/Akt/mTOR-signaling pathway is activated in AMG9810-induced skin tumors.Carcinogenesis.2011 May;32(5):779-85 |
 The Akt/mTOR signal pathway is activated by AMG9810in vivo.Carcinogenesis.2011 May;32(5):779-85 |
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