AMG 517

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Chemical Structure| 659730-32-2 同义名 : -
CAS号 : 659730-32-2
货号 : A593913
分子式 : C20H13F3N4O2S
纯度 : 99%+
分子量 : 430.4
MDL号 : MFCD14584859
存储条件:

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月

溶解度 : -
动物实验配方:

10% Tween 80+water 30 mg/mL suspension

生物活性
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
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

[1]Gavva NR, Bannon AW, 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.

[2]Doherty EM, Fotsch C, 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.

[3]Doherty EM, Fotsch C, Bannon AW, Bo Y, Chen N, Dominguez C, Falsey J, Gavva NR, Katon J, Nixey T, Ognyanov VI, Pettus L, Rzasa RM, Stec M, Surapaneni S, Tamir R, Zhu J, Treanor JJ, Norman MH. 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. doi: 10.1021/jm070190p. Epub 2007 Jun 22. PMID: 17585750.