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Sorafenib Tosylate

Cat. No. M1827
Sorafenib Tosylate Structure
Synonym:

BAY 43-9006,Nexavar

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mg USD 26.4  USD33 In stock
50mg USD 40  USD50 In stock
100mg USD 51.2  USD64 In stock
500mg USD 68.8  USD86 In stock
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Quality Control
Biological Activity

Sorafenib (BAY 43-9006) Tosylate is a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. A novel class of biaryl urea that inhibits C-RAF kinase was discovered using a combination of medicinal and combinatorial chemistry approaches. This effort culminated in the identification of the clinical candidate BAY 43-9006 (Sorafenib). Sorafenib inhibited the kinase activity of both C-RAF and B-RAF (wild type and V600E mutant). It inhibited MEK and ERK phosphorylation in various cancer cell lines and tumor xenografts and exhibited potent oral antitumor activity in a broad spectrum of human tumor xenograft models. Further characterization of sorafenib revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.

Product Citations
Customer Product Validations & Biological Datas
Source Drug Metab Dispos (2010). Figure 2. Sorafenib Tosylate
Method gastric gavage
Cell Lines Male FVB Tac-(KO)mdr1a-(KO)Mdr1b mice
Concentrations 5 ml/kg
Incubation Time
Results Distribution of radioactivity into the brain was also investigated 1 and 4 h after oral administration of 0.5 and 4 mg/kg [14C]sorafenib tosylate. Plasma concentrations were not affected by the knockout of P-gp
Source Drug Metab Dispos (2010). Figure 1. Sorafenib Tosylate
Method oral administration
Cell Lines Male FVB Tac-(KO)mdr1a-(KO)Mdr1b mice
Concentrations 0.5 and 4 mg/kg
Incubation Time 8 weeks
Results Whole brain concentrations in mdr1a/1b(-/-) mice 1 h after intravenous administration of 0.5 mg/kg [14C]sorafenib tosylate were statistically higher (p < 0.05) and showed a tendency toward higher concentrations at the other time points investigated compared with those in the WT mice
Protocol
Cell Experiment
Cell lines MDA-MB-231, Mia PaCa 2, HCT 116, LOX melanoma and pancreatic BxPC-3, NCI-H460 and A549 cell lines
Preparation method Tumor Cell Proliferation.
Tumor cells were trypsinized and plated in 96-well plates at 3000 cells per well in complete media with 10% FCS. Cells were incubated overnight at 37°C, and the next day, compounds were added in complete growth media over a final concentration range of 10 μmol/L to 10 nmol/L in 0.1% DMSO. Cells were incubated with test compounds for 72 hours at 37°C in complete growth media, and cell number was quantitated using the Cell TiterGlo ATP Luminescent assay kit (Promega). This assay measures the number of viable cells per well by measurement of luminescent signal based on amount of cellular ATP.
Concentrations 10 μmol/L to 10 nmol/L
Incubation time 72 h
Animal Experiment
Animal models MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, and A549 tumors xenograft model in Female NCr-nu/nu mice
Formulation Cremophor EL/ethanol (50:50; Sigma Cremophor EL, 95% ethyl alcohol)
Dosages 7.5, 15, 30 and 60 mg/kg, qd×9
Administration orally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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 Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 637.03
Formula C21H16ClF3N4O3.C7H8O3S
CAS Number 475207-59-1
Purity 100.0%
Solubility DMSO 30 mg/mL
Storage at -20°C
References

[1] Gradishar et al. Eur J Cancer. A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer.

[2] Kharaziha et al. Cancer Res. Sorafenib has potent anti-tumor activity in multiple myeloma in vitro, ex vivo and in vivo, in the 5T33MM mouse model.

[3] Mao et al. Acta Pharmacol Sin. The important roles of RET, VEGFR2 and the RAF/MEK/ERK pathway in cancer treatment with sorafenib.

[4] Eum et al. Mol Cell Biochem. Differential inhibitory effects of two Raf-targeting drugs, sorafenib and PLX4720, on the growth of multidrug-resistant cells.

[5] Wilhelm SM, 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.

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Keywords: Sorafenib Tosylate, BAY 43-9006,Nexavar supplier, VEGFR/PDGFR, inhibitors

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