Sorafenib Tosylate
Sorafenib tosylate, also named nexavar, is a small-molecule anticancer compound [1]. It is also a novel oral Raf kinase and a vascular endothelial growth factor receptor (VEGFR) inhibitor. It inhibits tumor cell proliferation and tumor angiogenesis [2]. To HepG2 cells (1× 106), the IC50 of sorafenib tosylate is 2.09μg/ml [3].
Raf is a mitogen-stimulated protein kinase that functions as a component of the signaling cascade that leads to the stimulation of mitogen-activated protein kinase [4].
Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells [5].
Treatment with nexavar potently inhibited the cell proliferation of MV4-11 cells (FLT3-ITD) in a dose-dependent manner with an IC50 of 0.88 nM. In MV4-11 cells, sorafenib tosylate of a concentration of 100 nM induced 43.6±5.2% of the cells to undergo apoptosis whereas in EOL-1 cells a concentration as low as 10 nM induced 89.29±1.8% of the cells to be apoptotic [6].
Nude rats at the age of 6 weeks injected with 105 MDA-MB-231 cells were involved. After monotherapy with sorafenib tosylate a significant reduction of the osteolytic lesion volume was observed on days 45 and 55 and of the soft tissue component volume on day 55 in comparison to untreated animals (p < 0.05). Compared to controls, treatment with sorafenib tosylate made bone metastases show significantly decreased values of Amplitude A and kep from day 35 to 55 (Amplitude A: p<0.01; kep p<0.01 on days 35 and 55; p<0.05 on day 45) [7].
References:
[1]. Chetan Lathia, John Lettieri, Frank Cihon, et al. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol, 2006, 57: 685-692.
[2]. M. J. Gnoth, S. Sandmann, K. Engel, et al. In Vitro to In Vivo Comparison of the Substrate Characteristics of Sorafenib Tosylate toward P-Glycoprotein. Drug Metabolism & Disposition, 2010, 38: 1341–1346.
[3]. Sayantan Dey, Subhadeep Roy, Nilanjana Deb, et al. Anti-carcinogenic Activity of Ruellia Tuberosa L. (Acanthaceae) Leaf Extract on Hepatoma Cell Line & Increased Superoxide Dismutase Activity on Macrophage Cell Lysate. Int J Pharm Pharm Sci, 2010, 5(Suppl 3): 854-861.
[4]. Markus Wartmann and Roger J. Davis. The Native Structure of the Activated Raf Protein Kinase Is a Membrane-bound Multi-subunit Complex. The Journal of Biological Chemistry, 1994, 269(9): 6695-6701.
[5]. Gera Neufeld, Tzafra Cohen, Stela Gengrinovitch, et al. Vascular endothelial growth factor (VEGF) and its receptors. The FASEB Journal, 1999, 13: 9-22.
[6]. D Auclair, D Miller, V Yatsula, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia, 2007, 21:439-445.
[7]. Maximilian Merz, Dorde Komljenovic, Stefan Zwick, et al. Sorafenib tosylate and paclitaxel induce anti-angiogenic, anti-tumour and anti-resorptive effects in experimental breast cancer bone metastases. European Journal of Cancer, 2011, 47:277-286.
- 1. Liao YJ, Hsu SM, et al. "Treatment with a New Barbituric Acid Derivative Exerts Antiproliferative and Antimigratory Effects against Sorafenib Resistance in Hepatocellular Carcinoma." Molecules. 2020;25(12):E2856. PMID:32575795
- 2. Suk FM, Liu CL, et al. "Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma." Sci Rep. 2019 Nov 21;9(1):17259. PMID:31754201
- 3. Ming-Hua Hsu, Shih-Ming Hsu, et al. "Treatment with low-dose sorafenib in combination with a novel benzimidazole derivative bearing a pyrolidine side chain provides synergistic anti-proliferative effects against human liver cancer." RSC Adv., 2017, 7, 16253-16263.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 637.03 |
| Cas No. | 475207-59-1 |
| Formula | C21H16ClF3N4O3·C7H8O3S |
| Solubility | ≥31.85 mg/mL in DMSO; insoluble in H2O; ≥4.15 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide;4-methylbenzenesulfonic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC=C(C=C1)S(=O)(=O)O.CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
MV4-11 and EOL-1 cells |
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Preparation method |
The solubility of this compound in DMSO is > 31.9 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
100 pM ~ 10 μM; 72 hrs for MV4-11 cells and 24 hrs for EOL-1 cells |
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Applications |
At a concentration of 100 nM, Sorafenib induced 43.6 ± 5.2% of the cells to undergo apoptosis. In EOL-1 cells, Sorafenib at a concentration as low as 10 nM promoted 89.29 ± 1.8% of the cells to undergo apoptosis. In addition, cell cycle analysis of Sorafenib-treated MV4-11 cells showed that Sorafenib dose-dependently induced cell cycle arrest with an increase in the percentages of cells in G0/G1 from 52.7 ± 0.9% (the control group) to 66.8 ± 1.5% (the 100 nM Sorafenib group). |
| Animal experiment [1]: | |
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Animal models |
Athymic mice bearing FLT3-ITD tumors |
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Dosage form |
0.3, 1.0, 3 or 10 mg/kg; p.o. |
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Applications |
In athymic mice bearing FLT3-ITD tumors, Sorafenib showed dose-dependent antitumor activity. At the doses of 3 and 10 mg/kg, 6 and 9 out of 10 mice showed complete responses, respectively. According to the Western blot analysis of MV4-11 tumors, phosphorylation of STAT5 was completely abolished 3 hrs after the second administration. Meanwhile, phospho-histone H3 was also significantly reduced. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. D Auclair, D Miller, V Yatsula, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia, 2007, 21:439-445. |
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| Description | Sorafenib Tosylate (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. | |||||
| Targets | Raf-1 | B-Raf | VEGFR2 | PDGFRβ | ||
| IC50 | 6 nM | 22 nM | 90 nM | 57 nM | ||
Quality Control & MSDS
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