AMG-517

製品コードS7115 バッチS711501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H13F3N4O2S
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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
10% Tween 80

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 10.000mg/ml (23.23mM) 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AMG-517は強力で選択的なTRPV1拮抗薬であり、カプサイシン、プロトン、および熱によるTRPV1の活性化をそれぞれIC50 0.76 nM、0.62 nM、1.3 nMで拮抗します。
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.
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. 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.
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.

プロトコル(参考用のみ)

キナーゼアッセイ Agonist-Induced 45Ca2+ Uptake Assay
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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/17652633/
  • https://pubmed.ncbi.nlm.nih.gov/18337008/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis [ Mucosal Immunol, 2024, S1933-0219(24)00006-0] PubMed: 38331094
Neuronal substance P-driven MRGPRX2-dependent mast cell degranulation products differentially promote vascular permeability [ Front Immunol, 2024, 15:1477072] PubMed: 39640264
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

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。