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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Purity: ≥98%
Regorafenib (also known as BAY 73-4506; BAY-73-4506) is a potent and orally bioavailable multi-kinase inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 values of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. It has antitumor properties and was given FDA approval to treat liver cancer.
Targets |
Raf-1 (IC50 = 2.5 nM); Tie2 (IC50 = 311 ± 46 nM); VEGFR2 (IC50 = 4.2 nM); VEGFR1 (IC50 = 13 nM); VEGFR2 (IC50 = 4.2 nM); BRafV600E (IC50 = 19 nM); PDGFRβ (IC50 = 22 nM); Braf (IC50 = 28 nM); VEGFR3 (IC50 = 46 nM)
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ln Vitro |
Regorafenib (0-10 μM, 96 h) exhibits anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375, and SW620 cells[1].
Regorafenib (0–3000 nM, 30 min) inhibits FGFR and pERK1/2 as well as the autophosphorylation of VEGFR2, TIE2, and PDGFR-β. Regorafenib has an IC50 of 5 μM and inhibits Hep3B cell growth in a concentration-dependent manner. Regorafenib then elevates phospho-c-Jun levels in Hep3B cells, a JNK target, but not total c-Jun levels[3]. |
ln Vivo |
Regorafenib (10 mg/kg, Orally, once or twice daily for 4 days) inhibits tumor growth and tumor vasculature in a rat GS9L glioblastoma model[1].
Regorafenib (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model[1]. |
Enzyme Assay |
In vitro assays using recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFRβ (aa561–aa1106), Raf-1 (aa305–aa648) and BRafV600E (aa409–aa765) kinase domains are performed. At a constant 1 μM Regorafenib concentration, the initial in vitro kinase inhibition profiling is carried out. Select responding kinases, such as VEGFR1 and RET, are used to calculate the 50% inhibitory concentration (IC50) values. Using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2, and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate, the homogeneous time-resolved fluorescence (HTRF) assay is used to measure TIE2 kinase inhibition.
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Cell Assay |
For proliferation tests, GIST 882 and TT cells are grown in RPMI medium with L-glutamine, while MDA-MB-231, HepG2, and A375 cells are grown in DMEM that is always supplemented with 10% high-fat b-casein sulfate. Trypsinized cells are plated at 5×104 cells per well in 96-well plates with complete media containing 10% FBS, and grown overnight at 37 °C. The incubation is continued for another 96 hours with the addition of vehicle or Regorafenib, serially diluted in complete growth media to final concentrations between 10 μM and 5 nM, and 0.2% DMSO. You can measure cell proliferation.
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Animal Protocol |
Female athymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O
3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg Orally |
References |
Molecular Formula |
C21H15CLF4N4O3
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Molecular Weight |
482.82
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Exact Mass |
482.07688
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Elemental Analysis |
C, 52.24; H, 3.13; Cl, 7.34; F, 15.74; N, 11.60; O, 9.94
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CAS # |
755037-03-7
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Related CAS # |
Regorafenib monohydrate;1019206-88-2;Regorafenib-d3;1255386-16-3;Regorafenib Hydrochloride;835621-07-3;Regorafenib mesylate;835621-08-4;Regorafenib-13C,d3
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Appearance |
Off-white to light pink solid powder
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SMILES |
CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F
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InChi Key |
FNHKPVJBJVTLMP-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
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Chemical Name |
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
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Synonyms |
BAY-734506; BAY734506; BAY 734506; Regorafenib. Brand name: Stivarga
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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 |
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: ≥ 7.5 mg/mL (15.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 75.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 2.75 mg/mL (5.70 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0712 mL | 10.3558 mL | 20.7117 mL | |
5 mM | 0.4142 mL | 2.0712 mL | 4.1423 mL | |
10 mM | 0.2071 mL | 1.0356 mL | 2.0712 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 |
NCT03042689 | Active Recruiting |
Drug: Regorafenib | Acute Myeloid Leukemia | Massachusetts General Hospital | April 17, 2017 | Phase 1 |
NCT03712943 | Active Recruiting |
Drug: Regorafenib Drug: Nivolumab |
Colon Cancer Colorectal Cancer Metastatic Colorectal Cancer |
H. Lee Moffitt Cancer Center and Research Institute |
October 23, 2018 | Phase 1 |
NCT04051606 | Active Recruiting |
Drug: Regorafenib | Recurrent Glioblastoma | Case Comprehensive Cancer Center |
July 31, 2019 | Phase 2 |
NCT04170556 | Active Recruiting |
Drug: Regorafenib Drug: Nivolumab |
Hepatocellular Carcinoma | Fundacion Clinic per a la Recerca Biomédica |
March 16, 2020 | Phase 1 Phase 2 |
NCT02098538 | Active Recruiting |
Drug: Regorafenib | Adenoid Cystic Carcinoma | Memorial Sloan Kettering Cancer Center |
March 2014 | Phase 2 |
Regorafenib inhibits key kinase targets in cells expressing VEGFR2, TIE2, PDGFR‐β, or FGFR.Int J Cancer.2011 Jul 1;129(1):245-55. td> |
Regorafenib inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model: time‐course analysis by DCE‐MRI.Int J Cancer.2011 Jul 1;129(1):245-55. td> |
Regorafenib significantly reduces tumor MVA in the Colo‐205 CRC xenograft model.Int J Cancer.2011 Jul 1;129(1):245-55. th> |
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Regorafenib exhibits antitumorigenic and antiangiogenic effects in the MDA‐MB‐231 breast xenograft model.Int J Cancer.2011 Jul 1;129(1):245-55. td> |
In vivoantitumor efficacy of regorafenib.Int J Cancer.2011 Jul 1;129(1):245-55. td> |