AMG9678 是一种有效的、选择性的、具有口服活性的TRPM8拮抗剂，IC50值为 31.2 nM。
| 生物活性 | AMG9678 is a potent, selective, orally active antagonist ofTRPM8with anIC50of 31.2 nM[1]. |
| IC50& Target | TRPM8 31.2 nM (IC50) | TRPA1 0.6 μM (IC50) |
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体外研究
(In Vitro) | AMG9678 potently inhibits the menthol and cold-induced increase in intracellular calcium in cells expressing rat TRPM8, the plasma half-life (T1/2) in rats is 7.6 h[1].
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体内研究
(In Vivo) | AMG9678 (0-100 mg/kg; p.o.; once) produces a significant and somewhat dose-dependent decrease in body temperature (Tb) in rats[1].
AMG9678 (30 mg/kg; p.o.; once daily for 4 consecutive days) decreases reduced body temperature after repeated dosing in rats[1].
| Animal Model: | Male Sprague Dawley rats weighing 200–350 g (6–12 weeks of age)[1] | | Dosage: | 10, 30 and 100 mg/kg | | Administration: | Oral administration, once or once daily for 4 consecutive days | | Result: | Produced a significant and somewhat dose-dependent decrease in Tbat 10, 30 and 100 mg/kg. The magnitude of TRPM8 blockade-induced decrease in body temperature is reduced after repeated dosing.
Effect of AMG9678 on Tbin rats. P value is for comparing compound administered rat Tbwith vehicle administered rat Tb. End of the study plasma concentration is reported in μM. Asterisk indicates one-way ANOVA followed by Dunnett's MCT
| Compound | Dose mg/kg (route) | Max Tbdecrease (℃) | Pvalue * | Time post dosing (min) | Plasma concentration | | AMG9678 | 10 (p.o.) | 0.72 | p< 0.001 | 60 | 0.04 ± 0.006 | | AMG9678 | 30 (p.o.) | 0.70 | p< 0.01 | 60 | 0.34 ± 0.1 | | AMG9678 | 100 (p.o.) | 0.83 | p< 0.05 | 60 | 0.36 ± 0.12 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
