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Purity: ≥98%
AMG 517 (AMG-517; AMG517) is a novel, potent and selective TRPV1 (vanilloid receptor-1) antagonist with potential anti-inflammatory activity. It antagonizes capsaicin, proton, and heat activation of TRPV1 with IC50 of 0.76 nM, 0.62 nM and 1.3 nM, respectively. The TRPV1 channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)α and possibly by other mechanisms. TRPV1 antagonists may decrease the resistance of older patients to infection and sepsis. When tested with stable CHO cell lines expressing TRPV1, treated with AMG-517 inhibited the activation of TRPV1.
| ln Vitro |
AMG 517 maintained efficacy in the capsaicin- and acid-mediated tests with IC50 values of 0.9 and 0.5 nM[1]. AMG 517 reduces capsaicin, pH 5, and heat-induced45Ca2+ uptake into cells expressing TRPV1 with IC50 values of 1 to 2 nM. AMG 517 inhibits capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells equally. AMG 517 suppresses native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 ± 0.2 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[2].
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| ln Vivo |
In a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED= 0.83 mg/kg, po) and a rodent "on-target" biochemical challenge model (capsaicin-induced flinch, ED50=0.33 mg/kg po), AMG 517 has been demonstrated to be effective[1]. The minimally effective dose of AMG 517 is 0.3 mg/kg, and the corresponding plasma concentration is 90 ng/mL. At 21 hours following CFA injection, oral administration of AMG 517 reverses established thermal hyperalgesia in a dose-dependent manner. AMG 517 induces brief hyperthermia in dogs, monkeys, and rodents. AMG 517 causes a high dose-dependent induction of hyperthermia; increases in body temperature of 0.5, 0.6, and 1.6°C are correlated with doses of 0.3, 1, and 3 mg/kg, respectively. Within 10 to 20 hours, the body temperatures of rats given all dosages of AMG 517 recover to baseline[2].
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| References |
[1]. Doherty EM, et al. Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate. J Med Chem. 2007 Jul 26;50(15):3515-27.
[2]. Gavva NR, et al. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J Pharmacol Exp Ther. 2007 Oct;323(1):128-37 |
| Molecular Formula |
C20H13F3N4O2S
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| Molecular Weight |
430.4
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| CAS # |
659730-32-2
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| SMILES |
S1C(N([H])C(C([H])([H])[H])=O)=NC2=C(C([H])=C([H])C([H])=C12)OC1C([H])=C(C2C([H])=C([H])C(C(F)(F)F)=C([H])C=2[H])N=C([H])N=1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3234 mL | 11.6171 mL | 23.2342 mL | |
| 5 mM | 0.4647 mL | 2.3234 mL | 4.6468 mL | |
| 10 mM | 0.2323 mL | 1.1617 mL | 2.3234 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.
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