Sorafenib (BAY 43-9006)

Biological Activity

Sorafenib (BAY 43-9006) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively. Sorafenib induces autophagy and apoptosis. Sorafenib has anti-tumor activity. Sorafenib is also a ferroptosis activator.

Product Citations

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  Cell Death Dis. 2020 Oct 23;11(10):902.

  The miR-30a-5p/CLCF1 axis regulates sorafenib resistance and aerobic glycolysis in hepatocellular carcinoma
  Sorafenib (BAY 43-9006) purchased from AbMole

• 

  J Virol. 2020 Feb 14;94(5):e01791-19.

  Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use
  Sorafenib (BAY 43-9006) purchased from AbMole

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  Phytomedicine. 2015 Dec 1;1139-49.

  Polyphyllin I induced-apoptosis is enhanced by inhibition of autophagy in human hepatocellular carcinoma cells.
  Sorafenib (BAY 43-9006) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Phytomedicine (2015). Figure 1. Sorafenib was purchased from AbMole (Shanghai, China)
	Method	Cell viability was determined by MTT assay
	Cell Lines	HCC HepG2
	Concentrations	0~100 µM
	Incubation Time	24, 48, 72 hours
	Results	PPI dose- and time-dependently inhibited the proliferation of HepG2 cells, with IC50 values of 1.047 ± 0.376µM within 24 h. Sorafenib was used as a positive control in HepG2 cells.

Protocol (for reference only)

Cell Experiment
Cell lines	PLC/PRF/5, Hep3B, HepG2, HuH7
Preparation method	PLC/PRF/5, Hep3B, HepG2 and HuH7 Cells were seeded in 96-well plates (3,000 cells/well) and incubated overnight for attachment, and were then treated with indicated agents in 10% FBS supplemented medium for 72 hours. The medium was replaced with MTT (0.5 mg/ml) at 37°C for 2 hours. After removal of medium, the cells were lysed with 200 μl per well dimethyl sulfoxide (DMSO), and absorbance at 570 nm was measured and the values of 50% inhibition concentration (IC50) for each drug were determined.
Concentrations	0, 0.25, 0.5,1, 2 µM
Incubation time	72 hours

Animal Experiment
Animal models	PLC/PRF/5 xenograft model in female athymic nude mice of 4–5 weeks of age
Formulation	Dissolved in Cremophor EL/ethanol (50:50; Sigma Cremophor EL, 95% ethanol) at 4 × concentration.
Dosages	60 mg/kg
Administration	Po, qd

Chemical Information

Molecular Weight	464.82
Formula	C21H16ClF3N4O3
CAS Number	284461-73-0
Solubility (25°C)	DMSO 45 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Qiujie Wang, et al. Cell Death Dis. GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis

[2] Jialei Sun, et al. Redox Biol. Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation

[3] Xin Chen, et al. Nat Rev Clin Oncol. Broadening horizons: the role of ferroptosis in cancer

[4] Scott M Wilhelm, et al. Cancer Res . 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

[5] Xiufeng Jiang, et,al. Oncotarget, Sorafenib and DE605, a novel c-Met inhibitor, synergistically suppress hepatocellular carcinoma