生物活性
CH5138303是一种口服有效的Hsp90抑制剂,其Kd为 0.48 nM。CH5138303 showed high binding affinity for N-terminal Hsp90α (Kd=0.52nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50=0.098μM, NCI-N87 IC50=0.066μM) and also displayed high oral bioavailability in mice (F=44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition=136%).
化学数据
分子量 | 415.9 |
分子式 | C19H18ClN5O2S |
CAS号 | 959763-06-5 |
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 |
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 |
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细胞系 | HCT116 and NCI-N87 cell lines |
方法 | Culturing HCT116 cell line and NCI-N87 cell line according to the supplier’s instructions. Suspending cells in a medium are added to solutions which contains various concentrations of the test substance, and culturing the cells at 37 °C in 5% CO2. Four days later, adding cell Counting Kit-8 solution and measuring absorbance at 450 nm with Microplate-Reader iMark. Calculating antiproliferative activity by the formula (1–T/C) × 100 (%), where T represents the absorbance of drug-treated cells and C that of untreated control cells at 450 nm. Using Microsoft Excel 2007 to calculate the 50% inhibition concentration (IC50) values |
浓度 | ~10 μM |
处理时间 | 4 days |
动物实验 |
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动物模型 | Mice with human NCI-N87 gastric cancer xenograft. |
配制 | |
剂量 | 50 mg/kg |
给药处理 | p.o. |
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Km系数(3),再除以大鼠的Km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
以下数据基于产品分子量,对于特殊产品,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 |
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1 mM | 2.4044 mL | 12.0221 mL | 24.0442 mL |
5 mM | 0.4809 mL | 2.4044 mL | 4.8088 mL |
10 mM | 0.2404 mL | 1.2022 mL | 2.4044 mL |