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Sorafenib tosylate

Name: Sorafenib tosylate
Brand: Selleck Chemicals
SKU: S1040
Rating: 5 (269 reviews)

Synonyms: BAY 43-9006 tosylate,NSC-724772 tosylate

Catalog No.S1040 Purity:99.99%

Sorafenib tosylate is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.

Sorafenib tosylate Chemical Structure

CAS No. 475207-59-1

Purity & Quality Control

Batch: Purity: 99.99%

99.99

Sorafenib tosylate Related Products

Related Targets	C-Raf/Raf-1 B-Raf A-raf	Click to Expand
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Related Compound Libraries	Kinase Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library Anti-alzheimer Disease Compound Library	Click to Expand

Signaling Pathway

Raf Signaling Pathway

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
MDA-MB-435	Growth Inhibition Assay	48 h	GI50=2 μM	22560627
UACC257	Growth Inhibition Assay	48 h	GI50=2 μM	22560627
MCF7	Growth Inhibition Assay	48 h	GI50=2.5 μM	22560627
EKVX	Growth Inhibition Assay	48 h	GI50=2.5 μM	22560627
HT-29	Growth Inhibition Assay	48 h	GI50=2.5 μM	22560627
SNB19	Growth Inhibition Assay	48 h	GI50=3.2 μM	22560627
OVCAR3	Growth Inhibition Assay	48 h	GI50=3.2 μM	22560627
CAKI-1	Growth Inhibition Assay	48 h	GI50=3.2 μM	22560627
SW620	Growth Inhibition Assay	48 h	GI50=3.2 μM	22560627
TK10	Growth Inhibition Assay	48 h	GI50=5 μM	22560627
endothelial precursor cells	Function assay		Inhibition of endothelial cord area formation in endothelial precursor cells by CD31 cord area detection based phenotypic drug discovery based assay, IC50 = 0.00421 μM.	22409666
Sf9	Function assay		Inhibition of GST-tagged recombinant human VEGFR2 expressed in Sf9 cells by radiometric assay, IC50 = 0.0125 μM.	24368209
endothelial precursor cells/ADSC cells	Toxicity assay		Toxicity in endothelial precursor cells co-cultured with stromal precursor ADSC cells by total nuclei count detection based phenotypic drug discovery based assay, EC50 = 5.46 μM.	22409666
endothelial precursor cells	Function assay		Inhibition of cell migration in endothelial precursor cells by Oris cell migration kit based phenotypic drug discovery based assay, IC50 = 16.7 μM.	22409666
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description

Targets

Raf-1 ^[1] (Cell-free assay)	VEGFR2/Flk1 ^[1] (Cell-free assay)	B-Raf ^[1] (Cell-free assay)	B-Raf (V599E) ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	Click to View More Targets
6 nM	15 nM	22 nM	38 nM	57 nM	Click to View More Targets

In vitro
In vitro	Sorafenib tosylate inhibits both wild-type and V599E mutant B-Raf activity with IC50 of 22 nM and 38 nM, respectively. Sorafenib tosylate also potently inhibits mVEGFR2 (Flk-1), mVEGFR3, mPDGFRβ, Flt3, and c-Kit with IC50 of 15 nM, 20 nM, 57 nM, 58 nM, and 68 nM, respectively. Sorafenib tosylate weakly inhibits FGFR-1 with IC50 of 580 nM. Sorafenib tosylate is not active against ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-Met, PKB, PKA, cdk1/cyclinB, PKCα, PKCγ, and pim-1. Sorafenib tosylate markedly inhibits VEGFR2 phosphorylation in NIH 3T3 cells with IC50 of 30 nM, and Flt-3 phosphorylation in HEK-293 cells with IC50 of 20 nM. Sorafenib tosylate potently blocks MEK 1/2 and ERK 1/2 phosphorylation in most cell lines but not in A549 or H460 cells, while having no effect on inhibition of the PKB pathway. Sorafenib tosylate inhibits the proliferation of HAoSMC and MDA-MB-231 cells with IC50 of 0.28 μM and 2.6 μM, respectively. ^[1] In addition to inhibition of the RAF/MEK/ERK signaling pathway, Sorafenib tosylate significantly inhibits the phosphorylation of eIF4E and down-regulates Mcl-1 levels in hepatocellular carcinoma (HCC) cells in a MEK/ERK-independent manner. Sorafenib tosylate inhibits the proliferation of PLC/PRF/5 and HepG2 cells with IC50 of 6.3 μM and 4.5 μM, respectively, and leads to the significant induction of apoptosis. ^[2]
Kinase Assay	Biochemical assays
Kinase Assay	Recombinant baculoviruses expressing Raf-1 (residues 305–648) and B-Raf (residues 409–765) are purified as fusion proteins. Full-length human MEK-1 is generated by PCR and purified as a fusion protein from Escherichia coli lysates. Sorafenib tosylate is added to a mixture of Raf-1 (80 ng), or B-Raf (80 ng) with MEK-1 (1 μg) in assay buffer [20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl₂, and 0.15% β-mercaptoethanol] at a final concentration of 1% DMSO. The Raf kinase assay (final volume of 50 μL) is initiated by adding 25 μL of 10 μM γ[³³P]ATP (400 Ci/mol) and incubated at 32 °C for 25 minutes. Phosphorylated MEK-1 is harvested by filtration onto a phosphocellulose mat, and 1% phosphoric acid is used to wash away unbound radioactivity. After drying by microwave heating, a β-plate counter is used to quantify filter-bound radioactivity. Human VEGFR2 (KDR) kinase domain is expressed and purified from Sf9 lysates. Time-resolved fluorescence energy transfer assays for VEGFR2 are performed in 96-well opaque plates in the time-resolved fluorescence energy transfer format. Final reaction conditions are as follows: 1 to 10 μM ATP, 25 nM poly GT-biotin, 2 nM Europium-labeled phospho (p)-Tyr antibody (PY20), 10 nM APC, 1 to 7 nM cytoplasmic kinase domain in final concentrations of 1% DMSO, 50 mM HEPES (pH 7.5), 10 mM MgCl₂, 0.1 mM EDTA, 0.015% Brij-35, 0.1 mg/mL BSA, and 0.1% β-mercaptoethanol. Reaction volumes are 100 μL and are initiated by addition of enzyme. Plates are read at both 615 and 665 nM on a Perkin-Elmer VictorV Multilabel counter at ~1.5 to 2.0 hours after reaction initiation. Signal is calculated as a ratio: (665 nm/615 nM) × 10,000 for each well. For IC50 generation, Sorafenib tosylate is added before the enzyme initiation. A 50-fold stock plate is made with Sorafenib tosylate serially diluted 1:3 in a 50% DMSO/50% distilled water solution. Final Sorafenib tosylate concentrations range from 10 μM to 4.56 nM in 1% DMSO.
Cell Research	Cell lines	MDA-MB-231, and HAoSMC
	Concentrations	Dissolved in DMSO, final concentrations ~10 μM
	Incubation Time	72 hours
	Method	Cells are exposed to increasing concentrations of Sorafenib tosylate for 72 hours. Cell number is quantitated using the Cell TiterGlo ATP Luminescent assay kit. This assay measures the number of viable cells per well by measurement of luminescent signal based on amount of cellular ATP.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	LC3-I / LC-3II / ATG5 p-STAT3 / STAT3/ Mcl-1 β-catenin / Survivin / Mcl-1 / PTMA pERK / ERK p-PKM2(Y105) / PMK2 / Caspase-9 RET(pY1016) / VEGFR2(pY1214) / MEK1(pT292) / ERK(pY204) Cyclin D1		23392173
	Immunofluorescence	p65 cytochrome c		22286758
	Growth inhibition assay	Cell viability		26039995
	ELISA	TGF-beta / CD206 Caspase-9 / Caspase-3		26158762

In Vivo
In vivo	Oral administration of Sorafenib tosylate (~60 mg/kg) demonstrates broad spectrum, dose-dependent anti-tumor activity against a variety of human tumor xenograft models including MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, and A549, with no evidence of toxicity. In association with the anti-tumor efficacy, Sorafenib tosylatetreatment potently inhibits MEK 1/2 phosphorylation and pERK 1/2 levels in HT-29 and MDA-MB-231 xenografts but not in Colo-205 xenografts, and significantly suppresses tumor microvessel area (MVA) and microvessel density (MVD) in MDA MB-231, HT-29 and Colo-205 tumor xenografts. ^[1] Sorafenib tosylate treatment produces dose-dependent growth inhibition of PLC/PRF/5 tumor xenografts in SCID mice with TGIs of 49% and 78% at 10 mg/kg and 30 mg/kg, respectively, consistent with the inhibition of ERK and eIF4E phosphorylation, reduction of the microvessel area, and induction of tumor cell apoptosis. ^[2]
Animal Research	Animal Models	Female NCr-nu/nu mice implanted s.c. with MDA-MB-231, Colo-205, HT-29, H460, or A549 cells
	Dosages	~60 mg/kg
	Administration	Orally once daily

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05068752	Recruiting	Pancreas Cancer	HonorHealth Research Institute\|Bayer\|Genentech Inc.	October 28 2021	Phase 2
NCT04763408	Active not recruiting	Carcinoma Hepatocellular	Eisai Inc.	April 9 2021	--

References

Chemical Information & Solubility

Molecular Weight	637.03	Formula	C₂₁H₁₆ClF₃N₄O₃.C₇H₈O₃S
CAS No.	475207-59-1	SDF	Download Sorafenib tosylate SDF
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
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 127 mg/mL ( (199.36 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 0.01 mg/mL

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Clear solution	saline	0.010mg/ml (0.02mM)	Taking the 1 mL working solution as an example, add 0.01 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.900mg/ml (7.69mM)	Taking the 1 mL working solution as an example, add 50 μL of 98 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify; add 50 μL Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.900mg/ml (7.69mM)	Taking the 1 mL working solution as an example, add 50 μL of 98 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	0.010mg/ml (0.02mM)	Taking the 1 mL working solution as an example, add 0.01 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	0.010mg/ml (0.02mM)	Taking the 1 mL working solution as an example, add 0.01 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	0.010mg/ml (0.02mM)	Taking the 1 mL working solution as an example, add 0.01 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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