生物活性
Trilaciclib(G1T28)是一种有效的,首创的 (first-in-class) CDK4/6 的可逆抑制剂,抑制CDK4/cyclin D1和CDK6/cyclin D3的IC50值分别为1 nM和4 nM。Trilaciclib (G1T28) protects RB competent cells from damage by chemotherapy as assessed by gamma-H2A.X (γH2AX) and apoptosis through caspase 3/7 activation in vitro and in vivo. In vivo, G1T28 regulates the proliferation of HSPCs in both mouse and canine bone marrow, in a reversible, doseand time-dependent manner.
化学数据
分子量 | 446.55 |
分子式 | C24H30N8O |
CAS号 | 1374743-00-6 |
纯度 | >99% |
溶解性(25°C) | Slightly soluble in water Slightly soluble in 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 | HS68 cells, WM2664 cells, A2058 cells |
方法 | HS68, WM2664 and A2058 cells are treated with 300 nM G1T28 or DMSO (0.1%), for 4, 8, 16 or 24 hours. Whole cell extracts are prepared using 1× radioimmunoprecipitation assay buffer (RIPA) containing 1× HALT protease and phosphatase inhibitors. Total protein concentration is determined by using the bicinchoninic acid (BCA) Protein Assay Kit, according to manufacturer's instructions. Fifteen micrograms of protein is heat denatured for 10 minutes at 70 ℃ and resolved by Novex NuPAGE SDS-PAGE gel system and transferred to 0.45 μm nitrocellulose membrane by electroblotting. |
浓度 | 10 nM, 30 nM, 100 nM, 300 nM, 1000 nM |
处理时间 | 4 h, 8 h, 16 h, 24 h |
动物实验 |
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动物模型 | 8-week-old female FVB mice |
配制 | 20% Solutol |
剂量 | 50 mg/kg, 100 mg/kg, 150 mg/kg |
给药处理 | oral gavage |
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 | 2.2394 mL | 11.197 mL | 22.3939 mL |
5 mM | 0.4479 mL | 2.2394 mL | 4.4788 mL |
10 mM | 0.2239 mL | 1.1197 mL | 2.2394 mL |