| Name | AMG 517 |
| Description | AMG 517 is an effective and specific TRPV1 antagonist, antagonizes proton (IC50: 0.76 nM), capsaicin (IC50: 0.62 nM), and heat activation (IC50: 1.3 nM) of TRPV1. |
| 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] |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 43 mg/mL (100 mM)
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| Keywords | Inhibitor | inhibit | Transient receptor potential channels | TRP Channel | AMG 517 |
| Inhibitors Related | (+)-Camphor | AP 18 | Methyl syringate | Caffeic Acid | Oleoyl Serotonin | (-)-Menthol | Camphor | Pregnenolone | Probenecid | 1,4-Cineole | Methyl salicylate | SKF-96365 hydrochloride |
| Related Compound Libraries | Bioactive Compound Library | Pain-Related Compound Library | Membrane Protein-targeted Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | Clinical Compound Library | Bioactive Compounds Library Max | Ion Channel Targeted Library | Anti-Cancer Drug Library |
United States
