生物活性
GSK461364抑制纯化的Plk1，Ki为2 nM，比作用于Plk2/3选择性高1000倍。GSK461364作用于非细胞分裂细胞，从多起点抑制癌细胞系增殖。 野生型p53的RNA沉默提高GSK461364的抗增殖活性。许多癌症疗法对p53野生型患者更有效, p53缺陷肿瘤对GSK461364的高度敏感性可提供治疗肿瘤的机会。
化学数据
| 分子量 | 543.6 |
| 分子式 | C27H28F3N5O2S |
| CAS号 | 929095-18-1 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 10 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 | MDA-MB-231, A549, and PC3 cell line |
| 方法 | Cell lines were obtained from American Type Culture Collection and grown in the recommended media at 37°C, 5% CO2 in a humidified incubator. Cells were plated in triplicate 96-well microtiter plates at 1,000 cells per well in culture media. GSK461364A dissolved in DMSO or negative control (0.1% DMSO) were added the following day, and one plate was harvested with 50 μL of CellTiter-Glo (Promega) for a time 0 (T = 0) measurement. Remaining duplicate cell plates were typically incubated for 72 h. Cells were then lysed with 50 μL CellTiter-Glo, and chemiluminescent signal was read on the Wallac EnVision 2100 plate reader. All data were normalized to signal at time of compound addition (T = 0). Curves were analyzed using the XLfit (IDBS Ltd.) curve-fitting tool for Microsoft Excel to determine the gI50 (concentration of 50% growth inhibition relative to T = 0 and Ymax values), the gI-maximum (concentration giving maximum growth inhibition), and the Ymin (bottom of the four-parameter curve at gI-maximum). |
| 浓度 | 0~10 μM |
| 处理时间 | 72 h |
| 动物实验 |
|---|
| 动物模型 | mice bearing Colo205 tumor xenograft model |
| 配制 | 4% DMA/Cremaphore (50:50), pH 5.6 |
| 剂量 | every 2 d (q2dx6, q2dx12) or every 4 d (q4dx3) at nominal dose levels of 25, 50, and 100 mg/kg/dose |
| 给药处理 | i.p. |
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 |
|---|
| 1 mM | 1.8396 mL | 9.1979 mL | 18.3959 mL |
| 5 mM | 0.3679 mL | 1.8396 mL | 3.6792 mL |
| 10 mM | 0.184 mL | 0.9198 mL | 1.8396 mL |
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