AMG-517

Catalog No.S7115 Batch:S711501

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Technical Data

Formula

C20H13F3N4O2S
Molecular Weight 430.4 CAS No. 659730-32-2
Solubility (25°C)* In vitro DMSO 86 mg/mL (199.81 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
10% Tween 80
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 10% Tween 80 clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description AMG 517 is a potent and selective TRPV1 antagonist, and antagonizes capsaicin, proton, and heat activation of TRPV1 with IC50 of 0.76 nM, 0.62 nM and 1.3 nM， respectively.
Targets
TRPV1 [1]
1 nM-2 nM
In vitro AMG 517 inhibits CAP- (500 nM), acid- (pH 5.0), or heat-(45 °C) induced 45Ca2+ influx into human TRPV1-expressing CHO Cells with IC50 of 0.76 nM, 0.62 nM and 1.3 nM. AMG 517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG 517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 nM. AMG 517 is a competitive antagonist of both rat and human TRPV1 with dissociation constant (Kb) values of 4.2 and 6.2 nM, respectively. AMG 517 is a highly selective TRPV1 antagonist. The IC50 value for AMG 517 is >20 μM against 2-APB-activated TRPV2 and TRPV3, 4-αPDD-activated TRPV4, allyl isothiocyanate-activated TRPA1, and icilin-activated TRPM8 in cell-based assays that measure agonist-induced increases in intracellular calcium in CHO cells recombinantly expressing the appropriate TRP channel. [1]
In vivo Oral administration of AMG 517 produces a dose-dependent increase in plasma concentrations, it also produces a dose-dependent decrease in the number of flinches induced by capsaicin treatment. The minimally effective dose (MED), based on a statistically significant difference in number of flinches from the vehicle versus capsaicin-administered group, is 0.3 mg/kg for AMG 517. The corresponding plasma concentrations are 90 to 100 ng/mL for AMG 517. AMG 517 (3 mg/kg) exhibits significant reductions in capsaicin-induced flinch up to 24 h after dosing. AMG 517 blocks thermal hyperalgesia in CFA model of pain.[1] AMG 517 elicits hyperthermia in rodents, dogs and monkeys but not in TRPV1 knockout mice. Interestingly, hyperthermia evoked by TRPV1-selective antagonists is attenuated after repeated dosing of these antagonists to rats, dogs and monkeys, and TRPV1 knockout mice does not exhibit an impairment of thermoregulation.[2]
Features Does not activate TRPV1 at concentrations ≤40 μM (measured by 45Ca2+ uptake into TRPV1-expressing cells), indicating that it is not a partial agonist.

Protocol (from reference)

Animal Study:[1]
  • Animal Models

    Male Sprague-Dawley rats

  • Dosages

    0.003-3 mg/kg

  • Administration

    p.o.

Selleck's AMG-517 has been cited by 10 publications

TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis [ Mucosal Immunol, 2024, S1933-0219(24)00006-0] PubMed: 38331094
The neural pathway of the hyperthermic response to antagonists of the transient receptor potential vanilloid-1 channel [ Temperature (Austin), 2023, 10(1):136-154] PubMed: 37187834
TRPV1+ sensory nerves modulate corneal inflammation after epithelial abrasion via RAMP1 and SSTR5 signaling [ Mucosal Immunol, 2022, 10.1038/s41385-022-00533-8] PubMed: 35680973
Cyclovirobuxine D, a cardiovascular drug from traditional Chinese medicine, alleviates inflammatory and neuropathic pain mainly via inhibition of voltage-gated Cav3.2 channels [ Front Pharmacol, 2022, 13:1081697] PubMed: 36618940
Electroacupuncture Pretreatment Elicits Neuroprotection Against Cerebral Ischemia-Reperfusion Injury in Rats Associated with Transient Receptor Potential Vanilloid 1-Mediated Anti-Oxidant Stress and Anti-Inflammation [ Inflammation, 2019, 10.1007/s10753-019-01040-y] PubMed: 31190106
Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats [Bai J, et al. Mol Pain, 2018, 14:1744806918777614] PubMed: 29768956
Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents. [ Anesthesiology, 2017, 127(5):813-823] PubMed: 28806222
Repurposing FDA-approved drugs for anti-aging therapies. [ Biogerontology, 2016, 17(5-6):907-920] PubMed: 27484416
Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury. [ Neural Regen Res, 2015, 10(8):1324-31] PubMed: 26487864
Released lipids regulate transient receptor potential channel (TRP)-dependent oral cancer pain. [ Mol Pain, 2015, 11:30] PubMed: 26007300

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.