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Sorafenib

SKU: orb1310944
FeaturedFeatured Product

Description

Sorafenib is an orally active multikinase inhibitor targeting Raf, VEGFR, PDGFRβ, and others, with IC50 values in the nanomolar range. It exhibits antitumor activity by inducing apoptosis, autophagy, and ferroptosis, making it a valuable tool for cancer research in both cellular and animal models.

Research Area

Cell Biology

Images & Validation

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Sorafenib

Key Properties

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CAS Number284461-73-0
MW464.83
Purity>98%
FormulaC21H16ClF3N4O3
SMILESO(C=1C=C(C(NC)=O)N=CC1)C2=CC=C(NC(NC3=CC(C(F)(F)F)=C(Cl)C=C3)=O)C=C2
TargetKinase
SolubilitySoluble in DMSO (up to 200 mg/ml) or in Ethanol (up to 3 mg/ml).

Bioactivity

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Target IC50
Huh7 cells:5.97 μM|PDGFRβ:57 nM (cell free)|B-Raf V599E:38 nM (cell free)|Flt3:58 nM|Raf-1:6 nM (cell free)|TPC1 cells:2.6 µM|Hep b3B cells:3.31 μM|BHT-101 cells:2.1 µM|c-Kit:68 nM (cell free)|B-CPAP cells:1.85 µM|HepG2 cells:7.42 μM|B-Raf:22 nM (cell free)|VEGFR2:90 nM|VEGFR3:20 nM (cell free)|FTC133 cells:2.9 µM
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In Vivo
METHODS: To assay antitumor activity in vivo, Sorafenib (7.5-60 mg/kg) was orally administered once daily for two to four days to NCr-nu/nu mice harboring human tumors MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, and A549. RESULTS: Sorafenib showed broad oral antitumor efficacy in various human tumor xenograft models. METHODS: To assay antitumor activity in vivo, Sorafenib (30 mg/kg/five times per week) and everolimus (10 mg/kg/three times per week) were administered by gavage to PTEN-mutant mice bearing CRPC, a tumor of desmoplasia-resistant prostate cancer, once a day for four weeks. RESULTS: Sorafenib administration increased the expression of androgen receptor p-GSK3β and p-ERK1/2 in CRPC, and the combination of Sorafenib and everolimus overcame treatment escape in CRPC tumors treated with Sorafenib alone.
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In Vitro
METHODS: Human hepatocellular carcinoma cells HepG2 and HuH-7 were treated with Sorafenib (2-20 µmol/L) for 48 h, and cell growth inhibition was detected using MTT method. RESULTS: Sorafenib dose-dependently inhibited the growth of HepG2 and HuH-7 cells with IC50 of approximately 6 µmol/L. METHODS: Human acute promyelocytic leukemia cells NB4 were treated with Sorafenib (1.5-12 µM) for 24-48 h. Apoptosis was detected using Flow Cytometry. RESULTS: Sorafenib dose-dependent apoptosis of NB4 cells, with a significant increase in the proportion of both early and late apoptotic cells. METHODS: Rat hepatobiliary cholangiocarcinoma cells LCC-2 were treated with Sorafenib (2.5-5 μM) for 12 h. Mitochondrial membrane potential was measured using JC-1 dye. RESULTS: Sorafenib depolarized the isolated mitochondria.
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Cell Research
Tumor cell lines were plated at 2 × 105 cells per well in 12-well tissue culture plates in DMEM growth media (10% heat-inactivated FCS) overnight. Cells were washed once with serum-free media and incubated in DMEM supplemented with 0.1% fatty acid-free BSA containing various concentrations of BAY 43-9006 in 0.1% DMSO for 120 minutes to measure changes in basal pMEK 1/2, pERK 1/2, or pPKB. Cells were washed with cold PBS (PBS containing 0.1 mmol/L vanadate) and lysed in a 1% (v/v) Triton X-100 solution containing protease inhibitors. Lysates were clarified by centrifugation, subjected to SDS-PAGE, transferred to nitrocellulose membranes, blocked in TBS-BSA, and probed with anti-pMEK 1/2 (Ser217/Ser221; 1:1000), anti-MEK 1/2, anti-pERK 1/2 (Thr202/Tyr204; 1:1000), anti-ERK 1/2, anti-pPKB (Ser473; 1:1000), or anti-PKB primary antibodies. Blots were developed with horseradish peroxidase (HRP)-conjugated secondary antibodies and developed with Amersham ECL reagent on Amersham Hyperfilm .
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Animal Research
Female NCr-nu/nu mice (Taconic Farms, Germantown, NY) were used for all studies. Three to five million cells were injected s.c. into the right flank of each mouse. DLD-1 tumors were established and maintained as a serial in vivo passage of s.c. fragments (3 × 3 mm) implanted in the flank using a 12-gauge trocar. A new generation of the passage was initiated every three weeks, and studies were conducted between generations 3 and 12 of this line. Treatment was initiated when tumors in all mice in each experiment ranged in size from 75 to 144 mg for antitumor efficacy studies and from 100 to 250 mg for studies of microvessel density and ERK phosphorylation. All treatment was administered orally once daily for the duration indicated in each experiment.
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Storage & Handling

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Storage-20°C
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

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BAY 43-9006

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Compound Identifiers

PubChem CID
216239 ↗

Key Properties

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No computed properties available.

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Sorafenib (orb1310944)

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