生物活性
BGT226 (NVP-BGT226)是一种新型I型PI3K/mTOR抑制剂,作用于PI3Kα/β/γ,IC50为4 nM/63 nM/38 nM。生长抑制实验显示NVP-BGT226具有抗肿瘤活性。NVP-BGT226显著抑制细胞生长,IC50 < 20 nM。NVP-BGT226在纳摩尔浓度时也诱导癌细胞凋亡,IC50≤25 nM。
化学数据
分子量 | 650.6 |
分子式 | C32H29F3N6O6 |
CAS号 | 1245537-68-1 |
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 | FaDu, Detroit 562, HONE-1 and HONE-1-C15 cells line |
方法 | Growth-inhibition assay. Cells in the logarithmic growth phase were cultured at a density of 5,000 to 20,000 cells per milliliter per well in a 24-well plate. The cells were exposed to various concentrations of BGT226 for 3 generation times. At the end of the incubation period, cells were fixed and stained with 50% ethanol containing 0.5% methylene blue for 30 minutes. The resulting colored residues were dissolved in 1% N-lauroyl-sarcosine, and optical density was read at 550 nm using a microplate reader. The IC50 value resulting from 50% inhibition of cell growth was calculated graphically as a comparison with control groups. Each point represents the average of at least 3 independent experiments run in duplicate. |
浓度 | IC50 ranging from 7.4 to 30.1 nmol/L |
处理时间 | 48 h |
动物实验 |
---|
动物模型 | human FaDu xenografted mice |
配制 | dissolved in 90% N-methyl-2-pyrrolidone (NMP)/10% PEG300 |
剂量 | 3.5 and 5mg/kg once a day for 21 consecutive days |
给药处理 | orally |
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 | 1.537 mL | 7.6852 mL | 15.3704 mL |
5 mM | 0.3074 mL | 1.537 mL | 3.0741 mL |
10 mM | 0.1537 mL | 0.7685 mL | 1.537 mL |