生物活性

TMC435350 (Simeprevir) is an oral HCV NS3/4A protease inhibitor. TMC435350 inhibited HCV replication in a cellular assay (subgenomic 1b replicon) with a half-maximal effective concentration (EC(50)) of 8 nM and a selectivity index of 5,875. In rats, TMC435350 was extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability was 44% after a single oral administration. TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. Data from phase I and II clinical trials of TMC-435350 (Simeprevir) have shown that TMC435350 is well tolerated as a once-daily oral therapy and provides potent antiviral activity in HCV genotype 1-infected subjects, with restoration of liver enzymes and no evidence of viral breakthrough.

化学数据

分子量	749.94
分子式	C38H47N5O7S2
CAS号	923604-59-5
纯度	>98%
溶解性（25°C）	DMSO
储存和运输条件	固体粉末： -20°C 冷藏长期储存 常温运输及临时存放

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

储备液配制

以下数据基于半岛bd体育手机客户端 分子量，对于特殊半岛bd体育手机客户端 ，请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.3334 mL	6.6672 mL	13.3344 mL
5 mM	0.2667 mL	1.3334 mL	2.6669 mL
10 mM	0.1333 mL	0.6667 mL	1.3334 mL