Sorafenib Tosylate (Bay 43-9006; Nexavar)

Alias: BAY 43-9006 tosylate; BAY549085; BAY-439-006; BAY 549085;BAY-439006 tosylate; BAY 439006; BAY439006 tosylate; BAY-549085; Nexavar; SFN
Cat No.:V1003 Purity: =99.89%
Sorafenib Tosylate (BAY439006; BAY-439006; BAY549085; BAY-549085; Nexavar; SFN), the tosylate salt of Sorafenib which is an approved anticancer medication, is a potent multi-kinase inhibitor of Raf-1, B-Raf and VEGFR-2 with potential antineoplastic activity.
Sorafenib Tosylate (Bay 43-9006; Nexavar) Chemical Structure CAS No.: 475207-59-1
Product category: Raf
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Sorafenib Tosylate (Bay 43-9006; Nexavar):

  • Sorafenib (Bay 43-9006)
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Purity & Quality Control Documentation

Purity: =99.89%

Purity: ≥98%

Product Description
Sorafenib Tosylate (BAY439006; BAY-439006; BAY549085; BAY-549085; Nexavar; SFN), a potent multi-kinase inhibitor of Raf-1, B-Raf, and VEGFR-2 with potential antineoplastic activity, is the tosylate salt of Sorafenib, an authorized anticancer drug. In enzymatic assays, its respective IC50 values for Raf-1, B-Raf, and VEGFR-2 are 6 nM, 22 nM, and 90 nM. In addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, preventing tumor angiogenesis. RAF kinase is a crucial enzyme in the RAF/MEK/ERK signaling pathway that regulates cell division and proliferation. Advanced renal cancer was given the go-ahead to be treated with sorafenib in 2005.
Biological Activity I Assay Protocols (From Reference)
Targets
VEGFR3 (IC50 = 20 nM); Braf (IC50 = 22 nM); Raf-1 (IC50 = 6 nM); VEGFR2 (IC50 = 90 nM); PDGFRβ (IC50 = 57 nM); BrafV599E (IC50 = 38 nM); c-Kit (IC50 = 68 nM); Flt3 (IC50 = 58 nM)
ln Vitro
Sorafenib Tosylate also inhibits BRAFwt (IC50=22 nM), BRAFV599E (IC50=38 nM), VEGFR-2 (IC50=90 nM), VEGFR-3 (IC50=20 nM), PDGFR-β (IC50=57 nM), c-KIT (IC50=68 nM), and Flt3 (IC50=58 nM) in biochemical assays[1].
Sorafenib Tosylate-induced phosphorylation of c-Met, p70S6K and 4EBP1 is significantly decreased when anti-human anti-HGF antibody is also given to 10-0505 cells, indicating that sorafenib tosylate treatment increases HGF secretion and activates c-Met and mTOR targets[2].
ln Vivo
Sorafenib Tosylate (10, 30, 50 and 100 mg/kg, orally) treatment inhibits the tumor growth of 06-0606 and 10-0505 xenografts in a dose-dependent manner (P<0.01). Sorafenib also significantly slows down the growth of the xenografts 06-0606 and 10-0505. The weights of 06-0606 tumors in mice receiving Sorafenib 50 mg/kg and 100 mg/kg treatments are roughly 13% and 5% of the controls, respectively. Sorafenib 50 mg dose significantly reduces tumor growth in mice with lines 5-1318, 26-1004, and 10-0505 (P<0.01). For a 50 mg dose, the T/C ratio for the 06-0606, 26-1004, 5-1318, and 10-0505 xenografts is 0.13, 0.10, 0.12, and 0.49, respectively, where T and C are the median weight (mg) of Sorafenib- and vehicle-treated tumors at the end of the treatment[2]. Compared to 100% in the normal control group, the survival rate is 73.3% in the Diethyl Nitrosamine (DENA) group and 83.3% in the Sorafenib group. While the treatment with Sorafenib results in a significant decrease (p<0.05) in liver index when compared to the DENA group, the DENA group exhibits a significant increase in liver index (1.51-fold increase, p<0.05) in comparison to the normal control group. The liver index significantly drops to a lower value in the Sorafenib group compared to the normal control group[3].
Enzyme Assay
Assay buffer, which contains 20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl2, and 0.15% β-mercaptoethanol, is used to combine Raf-1 (80 ng), wt BRAF (80 ng), or V599E BRAF (80 ng) with MEK-1 (1 μg) to test compound inhibition against different RAF kinase isoforms. After adding 25 μL of 10 μM γ-[33P]ATP (400 Ci/mol) to the 50 μL final volume of the RAF kinase assay, it is incubated at 32°C for 25 minutes. By filtration onto a phosphocellulose mat, phosphorylated MEK-1 is obtained. Unbound radioactivity is then removed using 1% phosphoric acid. Utilizing a β-plate counter, filter-bound radioactivity is measured after drying by microwave heating[1].
Cell Assay
The 10-0505, 06-0606, and 26-1004 tumors are finely minced and thoroughly washed three times in modified Eagle medium (MEM). Centrifuging at 800× g for 10 min is used to collect the cells. For 48 hours, cells are treated with 3 or 6 μM of sorafenib in serum-free MEM in the presence or absence of 5 μg/mL anti-human hepatocyte growth factor (HGF) antibody. Western blotting is used to determine the amount of HGF secreted in the conditioned medium after 2 mL of conditioned medium from animals treated with Sorafenib or the vehicle (without anti-human antibody) was collected and concentrated[2].
Animal Protocol
Mice: Four doses of sorafenib (10, 30, 50, and 100 mg/kg daily) are given orally to mice with the 06-0606 and 10-0505 xenografts for a dose-response experiment. The number of mice in each treatment group was five. Mice with tumors are given sorafenib 50 mg/kg orally once a day for 12 days in order to study the antitumor effects of the drug. Each experiment is repeated at least twice, and there are 14 animals in each treatment group. Seven days after the tumor was implanted, treatment began. The HCC xenografts had grown to a size of about 100 mm3 by this point. Mice with tumors (14 per group) are given 200 μL of vehicle, 50 mg/kg of Sorafenib, 1 mg/kg of Rapamycin, or Rapamycin plus Sorafenib orally once daily for the specified days in order to study the effects of Rapamycin plus Sorafenib on the growth of 10-0505 xenograft. Vernier caliper measurements of the tumor's length and width are used to track tumor growth at least twice per week. The formula for calculating tumor volume is [length×width2×π/6]. The mice are killed at the conclusion of the experiment, their body weights and tumor weights are noted, and the tumors are collected for examination. Rats: Male albino rats weighing 100–120 g are used in the experiment. Following the acclimatization period, rats are weighed and divided into three groups at random: For eight weeks, the vehicle is given daily to Group 1 (a normal control group; n = 10). 200 mg/kg of DENA is administered intravenously to Group 2 (the DENA group; n=15). Group 3 (Sorafenib group; n=12) receives Sorafenib orally twice daily for two weeks following DENA intravenously. Rats are weighed, put to sleep with ether, killed after the experiment (8 weeks), and then their livers are dissected. Two rounds of ice-cold saline washing and drying are performed on fresh liver before weighing. The formula for calculating liver index is liver weight (g)/final body weight (g) x 100. Five portions of the liver are removed, one of which is preserved in 10% formalin for histopathological analysis while the other four are immediately frozen in liquid nitrogen and kept at 80°C.
References

[1]. 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.

[2]. Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Cell Mol Med. 2009 Aug;13(8B):2673-83.

[3]. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med. 2016 Apr 16.

[4]. Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt. Am J Cancer Res. 2017 Dec 1;7(12):2503-2514.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C21H16CLF3N4O3.C7H8O3S
Molecular Weight
637.03
Exact Mass
637.020
Elemental Analysis
C, 52.79; H, 3.80; Cl, 5.56; F, 8.95; N, 8.80; O, 15.07; S, 5.03
CAS #
475207-59-1
Appearance
white solid powder
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
InChi Key
IVDHYUQIDRJSTI-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H16ClF3N4O3.C7H8O3S/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25;1-6-2-4-7(5-3-6)11(8,9)10/h2-11H,1H3,(H,26,30)(H2,28,29,31);2-5H,1H3,(H,8,9,10)
Chemical Name
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide;4-methylbenzenesulfonic acid
Synonyms
BAY 43-9006 tosylate; BAY549085; BAY-439-006; BAY 549085;BAY-439006 tosylate; BAY 439006; BAY439006 tosylate; BAY-549085; Nexavar; SFN
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~127 mg/mL (~199.4 mM)
Water: <1 mg/mL(slightly soluble or insoluble)
Ethanol: <1 mg/mL
Solubility (In Vivo)
2% Cremophor EL, 2% N,N-dimethylacetamide: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.5698 mL 7.8489 mL 15.6978 mL
5 mM 0.3140 mL 1.5698 mL 3.1396 mL
10 mM 0.1570 mL 0.7849 mL 1.5698 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02143401 Active
Recruiting
Drug: Sorafenib
Drug: Sorafenib Tosylate
Cirrhosis
Hepatitis B Infection
National Cancer Institute
(NCI)
November 7, 2014 Phase 1
NCT02185560 Active
Recruiting
Drug: Sorafenib Thyroid Carcinoma Bayer June 27, 2014
NCT01371981 Active
Recruiting
Drug: Asparaginase
Drug: Bortezomib
Leukemia Cutis
Myeloid Neoplasm
National Cancer Institute
(NCI)
June 20, 2011 Phase 3
NCT01817751 Active
Recruiting
Drug: sorafenib tosylate
Drug: valproic acid
Glioblastoma
Malignant Glioma
Virginia Commonwealth University April 11, 2013 Phase 2
NCT01187199 Active
Recruiting
Drug: Sorafenib
Drug: Paclitaxel
Advanced Cancer M.D. Anderson Cancer Center August 19, 2010 Phase 1
Biological Data
  • Sorafenib Tosylate

  • Sorafenib Tosylate
  • Sorafenib Tosylate

    The number of nuclei breaking the internal limiting membrane (ILM). A: Controlled group; B: ROP group; C: Vehicle-treated ROP group; D: Low doses sorafenib-treated ROP group; E: Middle doses sorafenib-treated ROP group; F: High dose sorafenib-treated ROP group.

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