受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C20H13F3N4O2S |
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分子量 | 430.4 | CAS No. | 659730-32-2 | ||||
Solubility (25°C)* | 体外 | DMSO | 86 mg/mL (199.81 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
製品説明 | 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. |
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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] |
特徴 | Does not activate TRPV1 at concentrations ≤40 μM (measured by 45Ca2+ uptake into TRPV1-expressing cells), indicating that it is not a partial agonist. |
キナーゼアッセイ | Agonist-Induced 45Ca2+ Uptake Assay | |
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Two days before the assay, cells are seeded in Cytostar 96-well plates at a density of 20,000 cells/well. The activation of TRPV1 and TRPV2 is followed as a function of cellular uptake of radioactive calcium. Capsaicin (0.5 μM), pH 5, and heat (45°C) are used as agonists for TRPV1, and 2-APB (200 μM) is used as the agonist for TRPV2. All of the antagonist 45Ca2+ uptake assays are conducted as reported previously and had a final 45Ca2+ concentration of 10 μCi/ml. Radioactivity is measured using a MicroBeta Jet. Data are analyzed using GraphPad Prism 4.01. | ||
動物実験 | 動物モデル | Male Sprague-Dawley rats |
投薬量 | 0.003-3 mg/kg | |
投与方法 | p.o. |
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TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis [ Mucosal Immunol, 2024, S1933-0219(24)00006-0] | PubMed: 38331094 |
Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway [ iScience, 2023, 26(5):106749] | PubMed: 37216091 |
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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