| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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| 2g |
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| 5g |
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| 10g |
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| 25g |
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| Other Sizes |
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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)
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| ln Vitro |
Sorafenib Tosylate also inhibits BRAFwt (IC50=22 nM), BRAFV599E (IC50=38 nM), VEGFR-2 (IC50=90 nM), VEGFR-3 (IC50=20 nM), PDGFR-β (IC50=57 nM), c-KIT (IC50=68 nM), and Flt3 (IC50=58 nM) in biochemical assays[1].
Sorafenib Tosylate-induced phosphorylation of c-Met, p70S6K and 4EBP1 is significantly decreased when anti-human anti-HGF antibody is also given to 10-0505 cells, indicating that sorafenib tosylate treatment increases HGF secretion and activates c-Met and mTOR targets[2]. |
| ln Vivo |
Sorafenib Tosylate (10, 30, 50 and 100 mg/kg, orally) treatment inhibits the tumor growth of 06-0606 and 10-0505 xenografts in a dose-dependent manner (P<0.01). Sorafenib also significantly slows down the growth of the xenografts 06-0606 and 10-0505. The weights of 06-0606 tumors in mice receiving Sorafenib 50 mg/kg and 100 mg/kg treatments are roughly 13% and 5% of the controls, respectively. Sorafenib 50 mg dose significantly reduces tumor growth in mice with lines 5-1318, 26-1004, and 10-0505 (P<0.01). For a 50 mg dose, the T/C ratio for the 06-0606, 26-1004, 5-1318, and 10-0505 xenografts is 0.13, 0.10, 0.12, and 0.49, respectively, where T and C are the median weight (mg) of Sorafenib- and vehicle-treated tumors at the end of the treatment[2]. Compared to 100% in the normal control group, the survival rate is 73.3% in the Diethyl Nitrosamine (DENA) group and 83.3% in the Sorafenib group. While the treatment with Sorafenib results in a significant decrease (p<0.05) in liver index when compared to the DENA group, the DENA group exhibits a significant increase in liver index (1.51-fold increase, p<0.05) in comparison to the normal control group. The liver index significantly drops to a lower value in the Sorafenib group compared to the normal control group[3].
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| Enzyme Assay |
Assay buffer, which contains 20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl2, and 0.15% β-mercaptoethanol, is used to combine Raf-1 (80 ng), wt BRAF (80 ng), or V599E BRAF (80 ng) with MEK-1 (1 μg) to test compound inhibition against different RAF kinase isoforms. After adding 25 μL of 10 μM γ-[33P]ATP (400 Ci/mol) to the 50 μL final volume of the RAF kinase assay, it is incubated at 32°C for 25 minutes. By filtration onto a phosphocellulose mat, phosphorylated MEK-1 is obtained. Unbound radioactivity is then removed using 1% phosphoric acid. Utilizing a β-plate counter, filter-bound radioactivity is measured after drying by microwave heating[1].
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| Cell Assay |
The 10-0505, 06-0606, and 26-1004 tumors are finely minced and thoroughly washed three times in modified Eagle medium (MEM). Centrifuging at 800× g for 10 min is used to collect the cells. For 48 hours, cells are treated with 3 or 6 μM of sorafenib in serum-free MEM in the presence or absence of 5 μg/mL anti-human hepatocyte growth factor (HGF) antibody. Western blotting is used to determine the amount of HGF secreted in the conditioned medium after 2 mL of conditioned medium from animals treated with Sorafenib or the vehicle (without anti-human antibody) was collected and concentrated[2].
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| Animal Protocol |
Mice: Four doses of sorafenib (10, 30, 50, and 100 mg/kg daily) are given orally to mice with the 06-0606 and 10-0505 xenografts for a dose-response experiment. The number of mice in each treatment group was five. Mice with tumors are given sorafenib 50 mg/kg orally once a day for 12 days in order to study the antitumor effects of the drug. Each experiment is repeated at least twice, and there are 14 animals in each treatment group. Seven days after the tumor was implanted, treatment began. The HCC xenografts had grown to a size of about 100 mm3 by this point. Mice with tumors (14 per group) are given 200 μL of vehicle, 50 mg/kg of Sorafenib, 1 mg/kg of Rapamycin, or Rapamycin plus Sorafenib orally once daily for the specified days in order to study the effects of Rapamycin plus Sorafenib on the growth of 10-0505 xenograft. Vernier caliper measurements of the tumor's length and width are used to track tumor growth at least twice per week. The formula for calculating tumor volume is [length×width2×π/6]. The mice are killed at the conclusion of the experiment, their body weights and tumor weights are noted, and the tumors are collected for examination.
Rats: Male albino rats weighing 100–120 g are used in the experiment. Following the acclimatization period, rats are weighed and divided into three groups at random: For eight weeks, the vehicle is given daily to Group 1 (a normal control group; n = 10). 200 mg/kg of DENA is administered intravenously to Group 2 (the DENA group; n=15). Group 3 (Sorafenib group; n=12) receives Sorafenib orally twice daily for two weeks following DENA intravenously. Rats are weighed, put to sleep with ether, killed after the experiment (8 weeks), and then their livers are dissected. Two rounds of ice-cold saline washing and drying are performed on fresh liver before weighing. The formula for calculating liver index is liver weight (g)/final body weight (g) x 100. Five portions of the liver are removed, one of which is preserved in 10% formalin for histopathological analysis while the other four are immediately frozen in liquid nitrogen and kept at 80°C.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation No information is available on the clinical use of sorafenib during breastfeeding. Because sorafenib is 99.5% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is 25 to 48 hours and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during sorafenib therapy and for 2 weeks after the last dose. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
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| Additional Infomation |
Sorafenib tosylate is an organosulfonate salt. It contains a sorafenib.
Sorafenib Tosylate is the tosylate salt of sorafenib, a synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis. A niacinamide and phenylurea derivative that inhibits multiple intracellular and cell surface kinases thought to be involved in ANGIOGENESIS, including RAF KINASES and VEGF RECEPTORS. It is used in the treatment of advanced RENAL CELL CARCINOMA and HEPATOCELLULAR CARCINOMA, and for treatment of THYROID CARCINOMA refractory to radioactive iodine therapy. See also: Sorafenib (has active moiety). Drug Indication Hepatocellular carcinomaNexavar is indicated for the treatment of hepatocellular carcinoma. Renal cell carcinomaNexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. Differentiated thyroid carcinomaNexavar is indicated for the treatment of patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma, refractory to radioactive iodine. |
| Molecular Formula |
C21H16CLF3N4O3.C7H8O3S
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|---|---|---|
| Molecular Weight |
637.03
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| Exact Mass |
636.105
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| Elemental Analysis |
C, 52.79; H, 3.80; Cl, 5.56; F, 8.95; N, 8.80; O, 15.07; S, 5.03
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| CAS # |
475207-59-1
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| Related CAS # |
Sorafenib;284461-73-0
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| PubChem CID |
406563
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| Appearance |
White solid powder
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| Density |
1.454 g/cm3
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| Boiling Point |
523.3ºC at 760 mmHg
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| Flash Point |
270.3ºC
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| LogP |
8.349
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
43
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| Complexity |
853
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(S(O)(=O)=O)C=C1.CNC(C1C=C(OC2=CC=C(NC(NC3=CC(C(F)(F)F)=C(Cl)C=C3)=O)C=C2)C=CN=1)=O
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| InChi Key |
IVDHYUQIDRJSTI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H16ClF3N4O3.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h2-11H,1H3,(H,26,30)(H2,28,29,31);2-5H,1H3,(H,8,9,10)
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| Chemical Name |
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide;4-methylbenzenesulfonic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (3.27 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% Cremophor EL, 2% N,N-dimethylacetamide: 30 mg/mL Solubility in Formulation 5: 5 mg/mL (7.85 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5698 mL | 7.8489 mL | 15.6978 mL | |
| 5 mM | 0.3140 mL | 1.5698 mL | 3.1396 mL | |
| 10 mM | 0.1570 mL | 0.7849 mL | 1.5698 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.
Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate
CTID: NCT00265798
Phase: Phase 2 Status: Active, not recruiting
Date: 2024-08-21
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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. |
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