Size | Price | Stock | Qty |
---|---|---|---|
50mg |
|
||
100mg |
|
||
500mg |
|
||
1g |
|
||
2g |
|
||
5g |
|
||
10g |
|
||
Other Sizes |
|
Purity: ≥98%
Targets |
VEGFR3 (IC50 = 20 nM); Braf (IC50 = 22 nM); Raf-1 (IC50 = 6 nM); VEGFR2 (IC50 = 90 nM); PDGFRβ (IC50 = 57 nM); BrafV599E (IC50 = 38 nM); c-Kit (IC50 = 68 nM); Flt3 (IC50 = 58 nM)
|
---|---|
ln Vitro |
Sorafenib's IC50 values of 22 nM and 38 nM, respectively, inhibit both wild-type and V599E mutant B-Raf activity. Additionally, mVEGFR2 (Flk-1) as well as mVEGFR3, mPDGFRβ, Flt3, and c-Kit are all potently inhibited by sorafenib, with respective IC50 values of 15 nM, 20 nM, 57 nM, 58 nM, and 68 nM. Sorafenib has a 580 nM IC50 and only moderately inhibits FGFR-1. Sorafenib tosylate is ineffective against the following targets: ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-Met, PKB, PKA, cdk1/cyclinB, PKCα, PKCγ, and pim-1. In NIH 3T3 cells, sorafenib significantly reduces VEGFR2 phosphorylation with an IC50 of 30 nM, and Flt-3 phosphorylation in HEK-293 cells with an IC50 of 20 nM. In most cell lines, sorafenib potently inhibits MEK 1/2 and ERK 1/2 phosphorylation, but not in A549 or H460 cells. It has no impact on the PKB pathway's inhibition. Sorafenib has an IC50 of 0.28 μM and 2.6 μM, respectively, and prevents HAoSMC and MDA-MB-231 cells from proliferating. [1] Sorafenib also significantly inhibits the phosphorylation of eIF4E and down-regulates Mcl-1 levels in hepatocellular carcinoma (HCC) cells in a MEK/ERK-independent manner, in addition to inhibiting the RAF/MEK/ERK signaling pathway. With IC50 values of 6.3 μM and 4.5 μM, respectively, sorafenib inhibits the proliferation of PLC/PRF/5 and HepG2 cells and significantly induces apoptosis.[2]
|
ln Vivo |
Sorafenib (60 mg/kg) administered orally exhibits no toxicity and broad spectrum, dose-dependent anti-tumor activity against a number of human tumor xenograft models, including MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, and A549. Sorafenib treatment significantly reduces tumor microvessel area (MVA) and microvessel density (MVD) in MDA MB-231, HT-29, and Colo-205 tumor xenografts, which is associated with its anti-tumor efficacy. However, it has no effect on MEK 1/2 phosphorylation or pERK 1/2 levels in HT-29 or MDA-MB-231 xenografts.[1] In SCID mice, sorafenib treatment results in a dose-dependent growth inhibition of PLC/PRF/5 tumor xenografts with TGIs of 49% and 78% at 10 mg/kg and 30 mg/kg, respectively. This is consistent with the inhibition of ERK and eIF4E phosphorylation, reduction of the microvessel area, and induction of tumor cell apoptosis. [2] By inhibiting NF-B mediated Mcl-1 and cIAP2 expression, sorafenib sensitizes bax-/- cells to TRAIL in a dose-dependent manner. In TRAIL-resistant HCT116 bax-/- and HT29 tumor xenografts, sorafenib (30–60 mg/kg) and TRAIL (5 mg/kg) showed dramatic efficacy. [3]
|
Enzyme Assay |
Raf-1 (80 ng), wt BRAF (80 ng), or V599E BRAF (80 ng) are mixed with MEK-1 (1 μg) in the assay buffer (20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl2, and 0.15% β-mercaptoethanol) to test the effects of the compound on different RAF kinase isoforms. Adding 25 μL of 10 μM γ-[33P]ATP (400 Ci/mol) and incubating the mixture at 32°C for 25 minutes kickstarts the RAF kinase assay (final volume of 50 μL). By filtering phosphorylated MEK-1 onto a phosphocellulose mat, radioactivity that is not bound to the protein is removed. Phosphorylated MEK-1 is then harvested. Using a β-plate counter, filter-bound radioactivity is measured after drying by microwave heating.
|
Cell Assay |
For 72 hours, Sorafenib tosylate is infused into cells at progressively higher concentrations. The Cell TiterGlo ATP Luminescent assay kit is used to calculate the number of cells. This assay counts the number of live cells in each well by measuring the luminescent signal, which is dependent on the amount of cellular ATP.
|
Animal Protocol |
Mice: Female NCr-nu/nu mice are used. Mice bearing 75 to 150 mg tumors are treated orally with Sorafenib (7.5 to 60 mg/kg), administered daily for 9 days. In each model, Sorafenib produces dose-dependent tumor growth inhibition with no evidence of toxicity, as measured by increased weight loss relative to control animals or drug-related lethality. In parallel to the antitumor efficacy studies, additional groups of four mice bearing 100 to 200 mg tumors are treated orally with vehicle or Sorafenib (30 to 60 mg/kg), administered daily for 5 days, which is the shortest treatment duration producing complete tumor stasis in the treated groups.
Rats: Male albino rats weighing 100 to 120 g are used for the study. Rats are weighed and randomly split into three groups following an acclimatization period. For 8 weeks, the car is given daily to Group 1 (the healthy control group; n=10). An i.p. single dose of 200 mg/kg DENA is administered to Group 2 (the DENA group; n=15). Six weeks after receiving a DENA intravenously in Group 3 (the Sorafenib group; n=12), Sorafenib is administered orally at a dose of 10 mg/kg daily for two weeks. Rats are weighed, put to sleep with ether, killed at the conclusion of the experiment (8 weeks), and their livers are removed. Fresh liver is weighed after being dried on a clean paper towel and going through two ice-cold saline washes. The liver index is calculated using the formula liver weight (g)/final body weight (g)×100. |
References |
Molecular Formula |
C21H16CLF3N4O3
|
---|---|
Molecular Weight |
464.82
|
Exact Mass |
464.09
|
Elemental Analysis |
C, 54.26; H, 3.47; Cl, 7.63; F, 12.26; N, 12.05; O, 10.33
|
CAS # |
284461-73-0
|
Appearance |
white solid powder
|
SMILES |
CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
|
InChi Key |
MLDQJTXFUGDVEO-UHFFFAOYSA-N
|
InChi Code |
InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
|
Chemical Name |
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide
|
Synonyms |
BAY 43-9006; BAY-439-006; BAY439006; BAY-439006; BAY 439006; BAY 549085; trade name: Nexavar; SFN
|
HS Tariff Code |
2934.99.9001
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
5%DMSO+45%PEG400+50%H2O: 0.375mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
|
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1514 mL | 10.7569 mL | 21.5137 mL | |
5 mM | 0.4303 mL | 2.1514 mL | 4.3027 mL | |
10 mM | 0.2151 mL | 1.0757 mL | 2.1514 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02185560 | Active Recruiting |
Drug: Sorafenib (Nexavar, BAY43-9006) |
Thyroid Carcinoma | Bayer | June 27, 2014 | |
NCT00265798 | Active Recruiting |
Drug: Sorafenib Tosylate | Gastrointestinal Stromal Tumor | National Cancer Institute (NCI) |
September 14, 2005 | Phase 2 |
NCT01817751 | Active Recruiting |
Drug: valproic acid Drug: sildenafil citrate |
Glioblastoma Malignant Glioma |
Virginia Commonwealth University | April 11, 2013 | Phase 2 |
NCT03412773 | Active Recruiting |
Drug: Tislelizumab Drug: Sorafenib |
Hepatocellular Carcinoma (HCC) |
BeiGene | December 28, 2017 | Phase 3 |
NCT01840592 | Active Recruiting |
Drug: Sorafenib Drug: Doxorubicin |
Hepatocellular Carcinoma | Memorial Sloan Kettering Cancer Center |
April 2013 | Phase 2 |
The number of nuclei breaking the internal limiting membrane (ILM). A: Controlled group; B: ROP group; C: Vehicle-treated ROP group; D: Low doses sorafenib-treated ROP group; E: Middle doses sorafenib-treated ROP group; F: High dose sorafenib-treated ROP group. td> |