生物活性
CX-4945 (Silmitasertib)是一种有效的,选择性CK2(casein kinase 2)抑制剂,IC50为1 nM,对Flt3, Pim1和CDK1作用效果稍弱(在细胞实验中无活性)。CX-4945是CK2特异的抑制剂,它只抑制238种激酶中的7种并且在0.5 μM浓度时它的抑制率超过90%,这是CK2的IC50的500多倍。虽然在无细胞系统中CX-4945抑制FLT3, PIM1和CDK1的IC50分别为35 nM, 46 nM和56 nM,但是在细胞基础上的功能实验中10 μM的CX-4945对FLT3, PIM1和 CDK1抑制作用不强。CX-4945有广谱的抗恶性细胞增生活性。
化学数据
分子量 | 349.77 |
分子式 | C19H12ClN3O2 |
CAS号 | 1009820-21-6 |
纯度 | 99.33% |
溶解性(25°C) | DMSO ≥ 46 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 |
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细胞系 | BT-474 (breast) or BxPC-3 (pancreatic) cancer or HUVEC cells |
方法 | A 5 mmol/L stock solution in dimethyl sulfoxide was prepared and stored at - 70 ℃. The drug was diluted directly into growth media immediately prior to use.Various cell lines were seeded at a density of 3,000 cells per well 24 hours prior to treatment, in appropriate media, and then treated with indicated concentrations of CX-4945. Suspensions cells were seeded and treated on the same day.Following 4 days of incubation, Alamar Blue (20 mL, 10% of volume per well) was added and the cells were further incubated at 37 C for 4–5 hours. Fluorescence with excitation wavelength at 530–560 nm and emission wavelength at 590 nm was measured. |
浓度 | 0, 0.1, 1.0, 5.0, 10 μM |
处理时间 | 24 h |
动物实验 |
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动物模型 | Female immunocompromised mice CrTac:Ncr-Foxn1nu (5–7 weeks old) BT474 or BxPC-3 cells Xenografts |
配制 | Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich). |
剂量 | twice daily at 25 or 75 mg/kg for 31 and 35 consecutive 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 | 2.859 mL | 14.2951 mL | 28.5902 mL |
5 mM | 0.5718 mL | 2.859 mL | 5.718 mL |
10 mM | 0.2859 mL | 1.4295 mL | 2.859 mL |