生物活性
LAQ824 (Dacinostat)是新型HDAC抑制剂,IC50为32 nM,且激活p21启动子。在体外, LAQ824抑制 H1299细胞裂解液中的人HDAC活性, IC50 为32 nM。此外, LAQ824通过激活p21 启动子,也激活编码p21 细胞周期抑制剂的基因表达,最大启动子活性 (AC50)为50%时,浓度为0.30 μM。 处理72小时后, LAQ824抑制 H1299(一种非小细胞肺癌细胞)和HCT116(一种结肠癌细胞)细胞生长,IC50分别为0.15 μM和 0.01 μM, LAQ824的抗增殖效果选择性作用于肿瘤细胞系。
化学数据
分子量 | 379.459 |
分子式 | C22H25N3O3 |
CAS号 | 404951-53-7 |
纯度 | >95% |
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, H1299, PC-3, DU145 and MDA435 cells |
方法 | Monolayer Growth Inhibition Assay.
Cell proliferation was measured using an adaptation of published procedures (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium assay) as described previously (29) . The CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay was performed according to the manufacturer’s protocol. The average background value (treatment with medium alone) was subtracted from each experimental well; triplicate values were averaged for each compound dilution. The following formulas were used to calculate the percentage of growth: The “% Growth” was plotted against compound concentration and used to calculate the IC50 using the linear regression techniques between data points to predict the concentration of compounds at 50% inhibition. |
浓度 | 0~10 μM |
处理时间 | 72 hr |
动物实验 |
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动物模型 | HCT116 cells tumor-bearing mice |
配制 | dissolved in DMSO to create a stock solution, which was further diluted just before dosing with D5W to a final DMSO concentration of 10%. |
剂量 | once daily, 5 days/week, for a total of 15 doses. |
给药处理 | i.v. injection into the tail vein |
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 | 2.6353 mL | 13.1767 mL | 26.3533 mL |
5 mM | 0.5271 mL | 2.6353 mL | 5.2707 mL |
10 mM | 0.2635 mL | 1.3177 mL | 2.6353 mL |