Sorafenib tosylate

SKU: orb1310945

Description

Sorafenib tosylate is a multikinase inhibitor with potent activity against targets including Raf-1, VEGFR-3, and B-Raf (IC50s: 6, 20, 22 nM, respectively). It is widely used in preclinical research for investigating oncogenic signaling pathways and has demonstrated antitumor effects in both cellular assays and animal models of various cancers.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 475207-59-1
• MW: 637.03
• Purity: 99.94% (May vary between batches)
• Formula: C₂₁H₁₆ClF₃N₄O₃·C₇H₈O₃S
• SMILES: Cc1ccc(cc1)S(O)(=O)=O.CNC(=O)c1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(c3)C(F)(F)F)cc2)ccn1
• Target: FLT,Autophagy,c-Kit,VEGFR,Ferroptosis,Raf,PDGFR,Apoptosis
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:200 mg/mL (313.96 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (7.85 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  PDGFRβ:57 nM (cell free)|B-Raf V599E:38 nM (cell free)|Raf-1:6 nM (cell free)|Flt3:58 nM|c-Kit:68 nM (cell free)|VEGFR2:90 nM|B-Raf:22 nM (cell free)|VEGFR3:20 nM (cell free)
• In Vivo:
  Sorafenib Tosylate, administered orally at doses of 10, 30, 50, and 100 mg/kg, dose-dependently inhibits the growth of 06-0606 and 10-0505 xenograft tumors, with significant efficacy (P<0.01). Particularly, in mice, Sorafenib at 50/100 mg/kg reduces the mass of 06-0606 tumors to about 13% and 5% of untreated controls, respectively. A 50 mg dose significantly curtails tumor expansion in the 5-1318, 26-1004, and 10-0505 lines (P<0.01). With this dose, the T/C ratio—an indicator of treatment effectiveness comparing the median weights of Sorafenib-treated and control tumors—significantly declines in these xenograft models, showcasing Sorafenib's potent anti-tumor activity. Furthermore, Sorafenib improves survival rates and markedly reduces the liver index (a measure of liver enlargement) in a model of liver damage induced by Diethylnitrosamine (DENA), demonstrating enhanced survival and liver condition in treated groups compared to both DENA-exposed and normal controls.
• In Vitro:
  Besides Raf-1, Sorafenib also inhibits VEGFR-3 (IC50: 20 nM), BRAF wt (IC50: 22 nM), B-RAF V599E (IC50: 38 nM), VEGFR-2 (IC50: 90 nM), PDGFR-β (IC50: 57 nM), c-KIT (IC50: 68 nM), and Flt3 (IC50: 58 nM) in biochemical assays . Sorafenib-induced phosphorylation of c-Met, p70S6K and 4EBP1 is significantly reduced when 10-0505 cells are co-treated with anti-human anti-HGF antibody, suggesting that treatment with Sorafenib leads to increased HGF secretion and activation of c-Met and mTOR targets .
• 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 .
• 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

FLT3, Ferroptosis, Fms like tyrosine kinase 3, Inhibitor, inhibit, mPDGFRβ, B-Raf (V599E), B-Raf, Apoptosis, Autophagy, Bay 43-9006, cKit, c-Kit, CD135, Cluster of differentiation antigen 135, Raf kinases, Raf, Raf-1, PDGFRβ, Sorafenib Tosylate, Sorafenib tosylate, Sorafenib, VEGFR, Vascular endothelial growth factor receptor, VEGFR2/Flk1

Compound Identifiers

PubChem CID

406563