| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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Purity: ≥98%
Regorafenib HCl, also known as BAY 73-4506, is a potent inhibitor of multiple kinases, including 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 is an orally bioavailable small molecule with anticancer activity that has received FDA approval for the treatment of liver cancer. In NIH-3T3/VEGFR2 cells, regulatorafenib prevents VEGFR2 autophosphorylation with an IC50 of 3 nM. Regorafenib, with an IC50 of 90 nM, inhibits PDGFR-β autophosphorylation in HAoSMCs following PDGF-BB stimulation. In MCF-7 breast cancer (BC) cells stimulated by FGF10, it also reduces FGFR signaling.
| Targets |
VEGFR1 (IC50 = 13 nM); VEGFR2 (IC50 = 4.2 nM); VEGFR3 (IC50 = 46 nM); PDGFRβ (IC50 = 22 nM); Braf (IC50 = 28 nM); VEGFR2 (BRafV600E = 19 nM); Raf-1 (IC50 = 2.5 nM)
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| ln Vitro |
Regorafenib potently inhibits VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with an IC50 of 3 nM. Regorafenib has an IC50 of 90 nM and blocks PDGFR-β autophosphorylation in HAoSMCs following PDGF-BB stimulation. With an IC50 of 3 nM, vegf165-stimulated HUVEC proliferation is inhibited by rogorafenib[1]. With a 5 μM IC50, regorafenib inhibits the growth of Hep3B cells in a concentration-dependent manner. The JNK target phospho-c-Jun, but not total c-Jun, is subsequently upregulated by regulatorafenib in Hep3B cells[3].
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| ln Vivo |
Regorafenib effectively slows the growth of Colo-205 xenografts at doses between 10 and 100 mg/kg, with a TGI of 75% at day 14 at the 10 mg/kg dose. Regorafenib is highly effective in the MDA-MB-231 model at doses as low as 3 mg/kg, producing a significant TGI of 81%, which rises to 93% at doses of 10 and 30 mg/kg, where tumor stasis is reached[1].
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| Enzyme Assay |
Recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFRβ (aa561–aa1106), Raf-1 (aa305–aa648) and BRafV600E (aa409–aa765) kinase domains are used in in vitro tests. At a constant 1 M 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 |
GIST 882 and TT cells are grown in RPMI medium with L-glutamine for proliferation assays, while MDA-MB-231, HepG2, and A375 cells are grown in DMEM that is always supplemented with 10% hiFBS. Trypsinized cells are plated at a density of 5×104 cells per well in 96-well plates containing 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. Using CellTitre-GloTM, cell proliferation is measured.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C₂₁H₁₆CL₂F₄N₄O₃
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| Molecular Weight |
519.28
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| Exact Mass |
518.0535584
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| CAS # |
835621-07-3
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| Related CAS # |
Regorafenib;755037-03-7;Regorafenib monohydrate;1019206-88-2
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| Appearance |
Solid
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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.Cl
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| InChi Key |
ACSWJKPZXNIVMY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H15ClF4N4O3.ClH/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);1H
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| Chemical Name |
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide;hydrochloride
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| Synonyms |
BAY-734506 HCl; BAY 734506; BAY734506; Regorafenib HCl. Brand name: Stivarga
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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: 2 mg/mL (3.85 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9257 mL | 9.6287 mL | 19.2574 mL | |
| 5 mM | 0.3851 mL | 1.9257 mL | 3.8515 mL | |
| 10 mM | 0.1926 mL | 0.9629 mL | 1.9257 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 |
| NCT03992456 | Active Recruiting |
Drug: Regorafenib Biological: Panitumumab |
Metastatic Colon Adenocarcinoma Metastatic Colorectal Carcinoma |
Academic and Community Cancer Research United |
April 24, 2020 | Phase 2 |
| NCT04776148 | Active Recruiting |
Drug: regorafenib Drug: lenvatinib |
Colorectal Neoplasms | Merck Sharp & Dohme LLC | March 29, 2021 | Phase 3 |
| NCT03563157 | Active Recruiting |
Drug: Oxaliplatin Drug: Regorafenib |
mCRC Colorectal Cancer Metastatic |
ImmunityBio, Inc. | May 25, 2018 | Phase 1 Phase 2 |
| NCT02788006 | Completed | Drug: Regorafenib 160 mg | Colorectal Adenocarcinoma | Federation Francophone de Cancerologie Digestive |
January 2016 | Phase 2 |
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Regorafenib inhibits key kinase targets in cells expressing VEGFR2, TIE2, PDGFR‐β, or FGFR.Int J Cancer.2011 Jul 1;129(1):245-55. |
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. |
Regorafenib significantly reduces tumor MVA in the Colo‐205 CRC xenograft model.Int J Cancer.2011 Jul 1;129(1):245-55. |
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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. |
In vivoantitumor efficacy of regorafenib.Int J Cancer.2011 Jul 1;129(1):245-55. |
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