Sorafenib

Catalog No.S7397 Batch:S739710

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Technical Data

Formula

C21H16ClF3N4O3
Molecular Weight 464.82 CAS No. 284461-73-0
Solubility (25°C)* In vitro DMSO 93 mg/mL (200.07 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Sorafenib is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib 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 induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
Targets
Raf-1 [1]
(Cell-free assay)		 mVEGFR2(Flk1) [1]
(Cell-free assay)		 mVEGFR3 [1]
(Cell-free assay)		 B-Raf [1]
(Cell-free assay)		 B-Raf (V599E) [1]
(Cell-free assay)		 View More
6 nM 15 nM 20 nM 22 nM 38 nM
In vitro Sorafenib inhibits both wild-type and V599E mutant B-Raf activity with IC50 of 22 nM and 38 nM, respectively. Sorafenib 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 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 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 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 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 significantly inhibits the phosphorylation of eIF4E and down-regulates Mcl-1 levels in hepatocellular carcinoma (HCC) cells in a MEK/ERK-independent manner. Sorafenib 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]
In vivo Oral administration of Sorafenib (~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 treatment 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 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] Sorafenib sensitizes bax-/- cells to TRAIL in a dose-dependent manner, through a mechanism involving down-regulating NF-κB 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]

Protocol (from reference)

Kinase Assay:

[1]
  • 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 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 Assay:

[1]
  • 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.
Animal Study:

[1]
  • 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

Customer Product Validation

Data from [Data independently produced by Mol Cancer Res, 2014, 12(10), 1377-87]

Data from [Data independently produced by Apoptosis, 2014, 19(4), 682-97]

Data from [Data independently produced by J Neurosci, 2013, 33(7), 3079-93]

Data from [Data independently produced by Mol Pharmacol, 2013, 84(4), 562-71]

Selleck's Sorafenib has been cited by 571 publications

METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma [ J Hematol Oncol, 2024, 17(1):78] PubMed: 39218945
Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer [ Cell Rep Med, 2024, S2666-3791(24)00201-5] PubMed: 38670097
PLAG1 interacts with GPX4 to conquer vulnerability to sorafenib induced ferroptosis through a PVT1/miR-195-5p axis-dependent manner in hepatocellular carcinoma [ J Exp Clin Cancer Res, 2024, 43(1):143] PubMed: 38745179
Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of hepatocellular carcinoma through ubiquitin-mediated degradation of SLTM and subsequent Notch pathway activation [ Cell Death Dis, 2024, 15(10):734] PubMed: 39384740
Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma [ Biomed Pharmacother, 2024, 173:116366] PubMed: 38458013
Morusin, a novel inhibitor of ACLY, induces mitochondrial apoptosis in hepatocellular carcinoma cells through ROS-mediated mitophagy [ Biomed Pharmacother, 2024, 180:117510] PubMed: 39341077
Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma [ J Transl Med, 2024, 22(1):593] PubMed: 38918793
Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways [ iScience, 2024, 27(6):110029] PubMed: 38883844
AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers [ Cancer Cell Int, 2024, 24(1):283] PubMed: 39135041
Network-based prediction of anti-cancer drug combinations [ Front Pharmacol, 2024, 15:1418902] PubMed: 39211773

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