生物活性
HA14-1是非肽类Bcl-2表面口袋配体,IC50为9 μM。HA14-1 is a small molecule which has the potential of inducing apoptosis in cancerous cells. HA14-1 manifests an antagonistic effect on antiapoptotic protein Bcl-2 and consequently induces cell death in various cancerous cell lines. HA-14-1 also has the ability to inhibit ceramide glucosyltransferase. The IC50 value of HA14-1 against ceramide glucosyltransferase is 4.5μM, which is lower than that reported for Bcl-2 in vitro. Kinetic analyses revealed that HA14-1 is a competitive and mixed-type inhibitor with respect to C6-NBD-ceramide and UDP-glucose, respectively.P53 pathway to be the probable mechanism of action for the induction of apoptosis in HeLa cell by downregulating the effect of anti-apoptotic proteins suggesting that HA14-1 may provide therapeutic potential for the treatment of human cervical cancer.
化学数据
分子量 | 409.23 |
分子式 | C17H17BrN2O5 |
CAS号 | 65673-63-4 |
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 |
---|
细胞系 | HF1A3, HF4.9 and HF28RA cells |
方法 | Determining the cytotoxic effects of HA14-1 against different FL cell lines by the MTT assay. Briefly, incubating the cells (5000/well) in triplicate in 96-well plate in the presence or absence of HA14-1 for 20 h at 37 °C. Thereafter, adding the MTT solution to each well. After 4 h incubation at 37 °C, measuring the optical density (OD) by means of 96-well plate reader, with the extraction buffer as a blank. The following formula is used: percentage cell viability = (OD of the experiment samples/OD of the control) ?100. Sigmoidal dose-response curves are fitted to the mean cell viability plotted against log HA14-1 dose and lethal concentration 50% (LC50) values are calculated from the resulting curves using Prism 4.0 softw |
浓度 | ~25 μM |
处理时间 | 20 h |
动物实验 |
---|
动物模型 | Female Swiss nude mice bearing BeGBM xenografts |
配制 | Free RPMI 1640-50% DMSO. |
剂量 | 400 nM |
给药处理 | Inject at the site of cell injection. |
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 | 2.4436 mL | 12.2181 mL | 24.4361 mL |
5 mM | 0.4887 mL | 2.4436 mL | 4.8872 mL |
10 mM | 0.2444 mL | 1.2218 mL | 2.4436 mL |