生物活性
GDC-0879是一种新型，有效的，选择性的B-Raf抑制剂，IC50为0.13 nM，对c-Raf也有抑制作用；对其他蛋白激酶没有抑制作用。体外研究，在V600E B-Raf 突变的A375黑色素瘤和V600E B-Raf突变的Colo205结肠癌细胞系中，GDC-0879抑制MEK1磷酸化作用时IC50分别为59和29 nM。GDC-0879有效抑制Malme3M细胞的B-raf V600E 酶促作用，IC50为0.75 μM。用GDC-0879处理，EC50值<0.5的细胞都表达B-raf V600E 致癌等位基因(A375,624,SK-MEL-28,Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34,及Colo201)。
化学数据
| 分子量 | 334.37 |
| 分子式 | C19H18N4O2 |
| CAS号 | 905281-76-7 |
| 纯度 | 99.68% |
| 溶解性（25°C） | DMSO 47 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 | A375 and Colo205 cells |
| 方法 | GDC-0879 in vitro IC50 estimates for pMEK inhibition were determined using A375 and Colo205 cells. In brief, A375 or Colo205 cells were incubated with a range of GDC-0879 concentrations (from 0.5 nM to 6.75 μM) for 25 min. Cells were lysed, and the lysates were subjected to centrifugation at 16,100g for 30 min, and the level of total protein was determined using the Bradford method (Bradford, 1976). Enzyme-linked immunosorbent assay kits were used to determine pMEK1 and total MEK1 protein levels in a 96-well format (Tago Biosource International, Camarillo, CA). Samples were analyzed in duplicate at 20 μg of protein per well according to the protocol of the supplier. The optical densities obtained at 450 nm were converted to units per milliliter (for pMEK1) or nanograms per milliliter (for total MEK1) using a standard curve determined with recombinant pMEK1 or MEK1. The pMEK1/total MEK1 ratios were then calculated as units per nanogram. The IC50 estimates for pMEK1 inhibition were estimated by nonlinear regression using GraphPad Prism version 4.02 (GraphPad Software Inc., San Diego, CA). |
| 浓度 | 0.5 nM to 6.75 μM |
| 处理时间 | 25 min |
| 动物实验 |
|---|
| 动物模型 | A375 and Colo205 tumor xenograft model |
| 配制 | 0.5% methylcellulose/0.2% Tween-80 (MCT) |
| 剂量 | A375 xenograft: 50, 100, 200mg/kg once daily / Colo205 xenograft:50, 100 mg/kg once daily |
| 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 |
|---|
| 1 mM | 2.9907 mL | 14.9535 mL | 29.907 mL |
| 5 mM | 0.5981 mL | 2.9907 mL | 5.9814 mL |
| 10 mM | 0.2991 mL | 1.4953 mL | 2.9907 mL |
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