同义名 :	Donafenib; Bay 43-9006-d3; CM-4307
	CAS号 :	1130115-44-4
	货号 :	A1213206
	分子式 :	C21H16ClF3N4O3
	纯度 :	98% 98%atom%D
	分子量 :	467.84
	MDL号 :	MFCD08460931
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

Donafenib, also known as CM-4307, is a multikinase inhibitor of Raf kinase and receptor tyrosine kinases with IC50 of 6 nM, 20 nM and 22 nM for Raf-1, B-Raf and VEGFR-3, respectively.[2]. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals[3].Sorafenib treatment induced the compensatory activation of the AKT pathway and autocrine VEGF in hepatoma cells, which could be reversed by celastrol. Furthermore, celastrol enhanced the growth inhibition and apoptosis induction of cancer cells by sorafenib both in vitro and in vivo and reduced the dosage of sorafenib needed[4].Changes in expression and genetic mutations of OATP1B1 significantly affected the uptake of sorafenib in HepG2 and LO2 transgenic cells, and the uptake of sorafenib was higher in HepG2 than LO2[5].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.14mL 0.43mL 0.21mL	10.69mL 2.14mL 1.07mL	21.37mL 4.27mL 2.14mL

参考文献

[1]Liu J, Li X, Zhang H, et al. Safety, pharmacokinetics and efficacy of donafenib in treating advanced hepatocellular carcinoma: report from a phase 1b trial. Pharmazie. 2019;74(11):688-693. [2] Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. [3] Yeonghoon Son, Na-Rae Shin,et al. Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells. Int J Mol Sci. 2021 May 19;22(10):5330. [4]Rui Zhang, Zhi Chen,et al. Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib. Med Sci Monit. 2019 Jun 1;25:4068-4075. [5]Jinhua Wen, Menghua Zhao. OATP1B1 Plays an Important Role in the Transport and Treatment Efficacy of Sorafenib in Hepatocellular Carcinoma. Dis Markers. 2021 Sep 26;2021:9711179.