Belinostat 别名：PXD101; PX105684; 贝利司他
Belinostat (PXD101)是一种新型的HDAC抑制剂，IC50为27 nM，对抵抗Cisplatin的肿瘤有效。
CAS No.：414864-00-9
化学性质/溶解性/储存
| 分子量 | 318.35 |
| 分子式 | C15H14N2O4S |
| CAS号 | 414864-00-9 |
| 中文名称 | 贝利司他 |
| 溶解性 | DMSO 60 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
生物活性
Belinostat (PXD101)是一种新型的HDAC抑制剂，IC50为27 nM，对抵抗Cisplatin的肿瘤有效。Belinostat抑制肿瘤细胞生长(包括A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3，及HS852)，IC50为0.2到0.66 μM。Belinostat 作用于A2780/cp70 和2780AD细胞时活性很低, 这两个细胞是抗cisplatin和doxorubicin的A2780细胞衍生的。Belinostat通过PARP分裂和组蛋白H3/H4的乙酰化而诱导细胞凋亡。
体内实验腹腔注射给药，配置方法（整理自公开文献，仅供参考）
1) For animal studies, belinostat was dissolved in L-Arginine to give a final concentration of 20 mg/ml. This formulation gave sufficient solubility for doses of ≤ 40 mg/kg.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2100044/
2) PXD101 was dissolved in DMSO (100 mg/ml for in vivo studies) and stored at -30 °C until experiments. For in vivo studies, PXD101 was further diluted with PBS to a final concentration of 8.6 mg/ml.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796495/
实验参考
下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| 浓度/溶剂体积/质量 | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 3.1412 mL | 15.706 mL | 31.412 mL |
| 5 mM | 0.6282 mL | 3.1412 mL | 6.2824 mL |
| 10 mM | 0.3141 mL | 1.5706 mL | 3.1412 mL |
*吸湿的DMSO对产品的溶解度有显著影响，请使用新开封的DMSO；
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
| 细胞系 | A2780, A2780/cp70, CALU-3, MCF7, PC3, HS852, HT29 and HCT116 cell lines |
| 方法 | Cytotoxicity Assay. Drug sensitivity was determined by a clonogenic assay (13). Briefly, cells were plated in 5 ml of medium at a density of 8 × 104 cells/25 cm2 flask and allowed to attach and grow for 48 h. Cells were exposed to drug (five concentrations from 0.016 to 10 μM) for 24 h. The medium was removed, and 1 ml of trypsin/EDTA was added to each flask. Once the cells had detached, 1 ml of medium was added, the cells were resuspended, and those from the control untreated flask were counted. Cells were diluted and plated into 6-cm Petri dishes (three per flask) at a density of 500-2000 cells/dish depending on the cell line. Cells from the drug-treated flasks were diluted and plated as for the control flasks. Dishes were incubated for 10–15 days at 37°C. Cells were washed with PBS, fixed in methanol, and stained with crystal violet, and colonies that contained ≥50 cells counted. Sensitivity is expressed as the IC50 (mean ± SE of three experiments) defined as the concentration of drug required to reduce the number of colonies to 50% of that of the control untreated cells. |
| 浓度 | 0.016 ~ 10 μM |
| 处理时间 | 24 h |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
建议您制定动物给药及实验方案时，尽量参考已发表的相关实验文献（溶剂种类及配比众多，简单地溶解目的化合物，并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题，未必能保证目的化合物在动物体内充分发挥生物学效用）。
体内实验的工作液，建议您现用现配，当天使用；如在配制过程中出现沉淀、析出现象，可以通过超声和（或）加热的方式助溶。
切勿一次性将产品全部溶解。
请在下面的计算器中，输入您的动物实验相关数据并点击计算，即可得到该实验的总需药量和工作液终浓度。
例如您给药剂量是10 mg/kg，平均每只动物的体重为20 g，每只动物的给药体积是100 μL，动物数量为20只，则该动物实验的总需药量为4 mg，工作液终浓度为2 mg/mL。
1：鉴于实验过程的损耗，建议您至少多配1-2只动物的量；
2：为该产品最终给药时的浓度。
| 动物模型 | A2780, A2780/cp70 and HCT116 tumor-bearing mice model |
| 配制 | dissolved in DMSO and then diluted in water to give a final concentration of DMSO of 10% |
| 剂量 | a single injection of 40 mg/kg |
| 给药处理 | i.p. |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
其他相关的HDAC产品
参考文献
