生物活性 | |||
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描述 | Vanilloid receptor-1 (TRPV1 or VR1), a well-characterized member of the transient receptor potential family of ion channels, has been implicated in the transmission of pain signaling[3]. AMG 517, a compound that potently blocks multiple modes of TRPV1 activation, shows potency in the capsaicin- and acid-mediated assays with IC50 values of 0.9 and 0.5 nM, respectively, while also processes excellent metabolic stability in human liver micosomes (CLin vitro < 5 μl/min/mg)[3]. In the capsaicin-induced hypothermia model in rats, AMG 517 was effective in a rodent on-target biochemical challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.). In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, AMG 517 showed dose-dependent inhibition of CFA-induced thermal hyperalgesia with efficacy at a minimum dose (MED) of 0.83 mg/kg (p.o.)[3]. | ||
作用机制 | Hydrogen-bond donor−acceptor interactions between the carbonyl oxygen, NH proton, and the aromatic nitrogen of AMG 517 and the receptor are critical for its optimum potency. |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.32mL 0.46mL 0.23mL |
11.62mL 2.32mL 1.16mL |
23.23mL 4.65mL 2.32mL |
参考文献 |
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