Sorafenib

SKU: orb1310944

Description

Sorafenib

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 284461-73-0
• MW: 464.82
• Purity: 99.69%
• Formula: C₂₁H₁₆ClF₃N₄O₃
• SMILES: O(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
• Target: Raf,Autophagy,Ferroptosis,PDGFR,c-Kit,FLT,Apoptosis,VEGFR
• Solubility: DMF:3.33 mg/mL (7.16 mM);DMSO:245 mg/mL (527.09 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5.9 mg/mL (12.69 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• 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
• 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 increase the expression of androgen receptor p-GSK3β and p-ERK1/2 in CRPC, an the combination of Sorafenib and everolimus overcame treatment escape in CRPC tumors treated with Sorafenib alone.
• 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 inhibite 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 depolarize the isolated mitochondria.
• 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 concentration 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 mM l/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:
  F Male NCr-nu/nu mice (Taconic Farms, Germantown, NY) were used for All studies. Three to five million cells were injected s.c. int 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 o 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 25 mg for studies of microvessel density and ERK phosphorylation. All treatment was administered orally once daily fo 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.
• Disclaimer: For research use only

Alternative Names

Sorafenib, PDGFRβ, Raf kinases, Raf-1, Raf, Vascular endothelial growth factor receptor, VEGFR, VEGFR2/Flk2, Ferroptosis, Fms like tyrosine kinase 3, FLT3, Inhibitor, mPDGFRβ, inhibit, B-Raf, B-Raf (V599E), Bay 43-9006, Autophagy, Apoptosis, CD135, Cluster of differentiation antigen 135, cKit, c-Kit

Compound Identifiers

PubChem CID

216239