GDC-0879

目录号 M1714 所有产品仅供科研使用，严禁用于人或动物的治疗等任何其他用途，不为任何个人提供产品和服务

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。

规格	价格	库存状态
Free Sample (0.5-1 mg)	¥ 0	中国库存现货
10mM*1mL in DMSO	¥ 750	中国库存现货
2mg	¥ 500	中国库存现货
5mg	¥ 700	中国库存现货
10mg	¥ 1100	中国库存现货
50mg	¥ 3400	中国库存现货

其他规格数量报价？

质量标准及产品资料

纯度： 99.68%
COA
MSDS
H-NMR
LC/MS

产品信息

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)。

产品使用成果展示

	数据来源	Mol Cancer Ther (2016). Figure 2. GDC-0879
	方法	Western blots
	细胞系/动物模型	BRAF WT, NRAS-mutant BRO melanoma cells
	浓度	100, 1000, 10000 nmol/L
	处理时间	24 h
	实验结果	In contrast, the tool compound GDC-0879 clearly induced formation of both CRAF/ARAF as well as CRAF/BRAF dimers. Nevertheless, BI 882370 induced phosphorylation of MEK1/2 and enhanced phosphorylation of ERK1/2 in BRO cells at concentrations between 3 and 300 nmol/L; importantly, however, expression of cyclins D1/D2 or Kip1/p27 was not affected

实验参考

体外实验*
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

*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。

体内实验*
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

*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。

化学性质

分子量	334.37
分子式	C19H18N4O2
CAS号	905281-76-7
溶解性（25°C）	DMSO 47 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。

储备液配制

*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。

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

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	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
K_m 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的K_m系数
	动物 A的K_m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K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Chou et al. J Pharm Biomed Anal. Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0879 and its metabolite in dog plasma using solid phase extraction.

[2] Choo et al. Xenobiotica. Disposition of GDC-0879, a B-RAF kinase inhibitor in preclinical species.

[3] Hoeflich et al. Cancer Res. Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression.

[4] Wong et al. J Pharmacol Exp Ther. Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy.

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