Item no. |
S1040-10000 |
Manufacturer |
Selleckchem
|
CASRN |
475207-59-1 |
Amount |
10 g |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
Bay 43-9006, Raf-1, B-Raf, VEGFR2, PDGFRbeta;Raf |
Similar products |
Sorafenib |
Available |
|
Administration |
Orally once daily |
Animal Models |
Female NCr-nu/nu mice implanted s.c. with MDA-MB-231, Colo-205, HT-29, H460, or A549 cells |
Cell lines |
MDA-MB-231, and HAoSMC |
Chemical Name |
2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-, 4-methylbenzenesulfonate (1:1) |
Clinical Trials |
Sorafenib sensitizes bax-/- cells to TRAIL in a dose-dependent manner, through a mechanism involving down-regulating NF-kappaB mediated Mcl-1 and cIAP2 expression. Combining Sorafenib (30-60 mg/kg) with TRAIL (5 mg/kg) show dramatic efficacy in TRAIL-resistant HCT116 bax-/- and HT29 tumor xenografts. [3] A Phase II study of Sorafenib combined with transarterial chemoembolization (TACE) in treating HBV-infected patients with intermediate hepatocellular carcinoma is currently ongoing. |
Concentrations |
Dissolved in DMSO, final concentrations ca.10 uM |
Description |
Sorafenib Tosylate (Bay 43-9006, Nexavar) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively. |
Dosages |
ca.60 mg/kg |
Formulation |
Dissolved in Cremophor EL/ethanol (50:50) as 4-fold (4x) stock solution, and diluted to 1x with water |
IC50 |
6 nM, 6 nM, 6 nM, 6 nM, 6 nM, 6 nM |
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, mPDGFRbeta, 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, PKCalpha, PKCgamma, 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 uM and 2.6 uM, 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 uM and 4.5 uM, respectively, and leads to the significant induction of apoptosis. [2] |
In vivo |
Oral administration of Sorafenib tosylate (ca.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] |
Incubation Time |
72 hours |
Kinase Assay |
Biochemical assays, 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 ug) in assay buffer [20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl2, and 0.15% beta-mercaptoethanol] at a final concentration of 1% DMSO. The Raf kinase assay (final volume of 50 uL) is initiated by adding 25 uL of 10 uM gamma[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 beta-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 pemed in 96-well opaque plates in the time-resolved fluorescence energy transfer format. Final reaction conditions are as follows: 1 to 10 uM 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% beta-mercaptoethanol. Reaction volumes are 100 uL and are initiated by addition of enzyme. Plates are read at both 615 and 665 nM on a Perkin-Elmer VictorV Multilabel counter at ca.1.5 to 2.0 hours after reaction initiation. Signal is calculated as a ratio: (665 nm/615 nM) x 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 uM to 4.56 nM in 1% DMSO. |
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. |
Molecular Weight (MW) |
637, 03 |
Picture ChemicalStructure Description |
Sorafenib (Nexavar) Chemical Structure |
Picture Description 1 |
, , Christina W Yde/CDM Danish Cancer Society Research Center Denmark, Sorafenib (Nexavar)purchased from Selleck, Inhibition of breast cancer cell growth using sorafenib. MCF-7 breast cancer cells were treated with increasing concentrations of sorafenib for 5 days. Cell number was measured using a colorimetric growth assay (crystal violet stain) and expressed relative to DMSO treated control cells. |
Picture Description 2 |
Data from [J Invest Dermatol , 2011, 131, 18861895], Sorafenib (Nexavar)purchased from Selleck, Inhibition of the MAPK signaling pathway results in downregulation of Plk-1 protein expression. (a) WB analysis for Plk-1 protein after treatment of human melanoma cell lines M14 and WM-115 with MEK 1/2 inhibitor PD98059 (10 M), JNK inhibitor (16 M), p38 inhibitor SB203580 (20 M), and multikinase inhibitor sorafenib (10 M) for 48 h showing significant reduction in the expression of Plk-1 protein after 48 hours. (b) Annexin V/PI staining of cells treated with MAPK inhibitors and induction of apoptosis. JNK, c-Jun N-terminal kinase, MAPK, mitogen-activated protein kinase, MEK 1/2, mitogen-activated protein kinase kinase 1/2, Plk-1, polo-like kinase 1, WB, western blot. |
Solubility (25C) |
DMSO 127 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.