同义名 :	ACT-709478
	CAS号 :	1838651-58-3
	货号 :	A1143293
	分子式 :	C22H18F3N5O
	纯度 :	99%+
	分子量 :	425.41
	MDL号 :	MFCD31813695
	存储条件：	Pure form Inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

T-type calcium channels (TTCCs) belong to the family of thelow-voltage-activated calcium channels. These channels are the products of three genes, CACNA1G, CACNA1H, and CACNA1I, yielding the Cav3.1, Cav3.2, and Cav3.3 channels, respectively. ACT-709478 blocked hCav3.3 potently but with marked voltage-dependency (Kr ≈ 1500 nM and Ki ≈ 20 nM). ACT-709478 blocked currents through hKv11.1-hERG channels with an IC50 of 5.5 μM. In WAG/Rij rats, 10 mg/kg po of ACT-709478 significantly decreased the cumulative duration of absence-like seizures over the next 12 h period by 93%, compared to a matched vehicle group. ACT-709478 completely suppressed the absence-type seizures over the first 6 h following administration. In the AGS model of juvenile DBA/2J mice, ACT-709478 showed a significant decrease of the seizure severity at a dose of 100 mg/kg po[1]. Ascending single oral doses of 1-400 mg ACT-709478 were administered to sequential groups of eight subjects. ACT-709478 exhibited good tolerability and safety after single-dose administration[2].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.35mL 0.47mL 0.24mL	11.75mL 2.35mL 1.18mL	23.51mL 4.70mL 2.35mL

参考文献
[1]Bezençon O, Heidmann B, Siegrist R, et al. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies. J Med Chem. 2017;60(23):9769‐9789 [2]Richard M, Kaufmann P, Kornberger R, Dingemanse J. First-in-man study of ACT-709478, a novel selective triple T-type calcium channel blocker. Epilepsia. 2019;60(5):968‐978