生物活性

Tipifarnib(R115777)是一种有效的，特异性farnesyltransferase(FTase)抑制剂，作用于H-ras或N-ras突变细胞，具有最显著的抗增殖作用效果。与DMSO处理的LGL T细胞相比，用5 μM Tipifarnib处理72小时，凋亡细胞百分率明显高很多。使用健康捐赠者提供的T细胞，Tipifarnib按剂量依赖性降低IFNγ阳性细胞百分率。在沉淀物中，与DMSO相比，Tipifarnib降低激活型Ras的数量。

化学数据

分子量	489.39
分子式	C27H22Cl2N4O
CAS号	192185-72-1
纯度	100.0%
溶解性（25°C）	DMSO 14 mg/mL
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

实验操作来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）

细胞实验
细胞系	MCF-7 cells line
方法	Cell Growth Assays. Steroid-depleted cells were seeded into 12-well plates at a density of ~1 × 104 cells per well or into 96-well plates at a density of 4,000 cells per well, in dextran-coated charcoal medium. After 24 h, monolayers were treated with E2 plus inhibitors either alone or in combination. The 12-well plates were treated for 6 days with daily changes. Cell number was then determined using a Z1 Coulter counter (Beckman Coulter). The 96-well plates were treated with a single dose and left for 96 h at which time cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as described previously (15). The interaction between R115777 and 4-OH-tamoxifen was analyzed by the median effect plot method described by Chou and Talalay (16). Calculation of the combination index took into account a nonfixed drug ratio and was based on the assumption that the action of the two drugs was mutually nonexclusive for the strict detection of synergism. A combination index< 1 indicates synergism, combination index = 1 indicates additivity, and a combination index >1 indicates antagonism. Experiments were repeated thrice.
浓度	0~1000 nM
处理时间	96 h

动物实验
动物模型	MCF-7 xenografts in Female ovariectomized Ncr foxhead nude mice
配制	20% w/v β-cyclodextrin (pH 2.5)
剂量	50 mg/kg twice daily for 5 consecutive days followed by a 2-day rest period, for a total of 19 days
给药处理	oral gavage

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	2.0434 mL	10.2168 mL	20.4336 mL
5 mM	0.4087 mL	2.0434 mL	4.0867 mL
10 mM	0.2043 mL	1.0217 mL	2.0434 mL