Home Protein Tyrosine Kinase VEGFR inhibitor - c-RET inhibitor - Autophagy activator - c-Kit inhibitor - Raf inhibitor - PDGFR inhibitor Regorafenib For research use only.

Regorafenib

Synonyms: Fluoro-Sorafenib, BAY 73-4506

Regorafenib is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy.

Regorafenib Chemical Structure

Regorafenib Chemical Structure

CAS No. 755037-03-7

Purity & Quality Control

Regorafenib Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Hep3B Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
PLC/PRF/5  Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
HepG2  Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
HEK293 Function Assay 0.5 μM 2/4/6 h reduces GRP78 expression 25858032
GEO Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
SW48 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
HT29 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
SW480 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
SW620 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
HCT116 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
LOVO Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
HCT150 Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
SW48-CR Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
GEO-CR Growth Inhibition Assay 0.01-20 μM 96 h DMSO inhibits cell growth in a dose-dependent manner 25838391
KB-31 Growth Inhibition Assay IC50=5.5±0.3 nM 25753361
KB-G2 Growth Inhibition Assay IC50=9.1±0.1 nM 25753361
LLC-PK1 Growth Inhibition Assay IC50=42.0±3.2 nM 25753361
LLC-PK1/MRP2 Growth Inhibition Assay IC50=82.4±2.7 nM 25753361
HEK293 Growth Inhibition Assay IC50=11.0±1.2 nM 25753361
HEK293/OATP1B1 Growth Inhibition Assay IC50=6.2±0.3 nM 25753361
HROC18 Growth Inhibition Assay IC50=1.3 μM 25309914
HROC24 Growth Inhibition Assay IC50=4.6 μM 25309914
HROC43 Growth Inhibition Assay IC50=5.3 μM 25309914
HROC46 Growth Inhibition Assay IC50=2.4 μM 25309914
RJ345 Function Assay 0.5/5 μM 24 h DMSO inhibits the cell migration 25253994
RJ348 Function Assay 0.5/5 μM 24 h DMSO inhibits the cell migration 25253994
MCF-7 Function Assay 0.5/5 μM 24 h DMSO inhibits the cell migration 25253994
MDA-MB-231 Function Assay 0.5/5 μM 24 h DMSO inhibits the cell migration 25253994
HT15 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
DLD1 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
HT-29 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
Hct-116 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
HT15 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
DLD1 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
HT-29 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
Hct-116 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
GBM5 Apoptosis Assay 0.5–1.0 μM 24 h DMSO interacts with lapatinib to induce cell death 24911215
GBM6 Apoptosis Assay 0.5–1.0 μM 24 h DMSO interacts with lapatinib to induce cell death 24911215
GBM12 Apoptosis Assay 0.5–1.0 μM 24 h DMSO interacts with lapatinib to induce cell death 24911215
GBM14  Apoptosis Assay 0.5–1.0 μM 24 h DMSO interacts with lapatinib to induce cell death 24911215
Hep3B Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
PLC/PRF/5  Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
HepG2  Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
HCT116  Function Assay 10/20/40 μM 24 h induces PUMA protein and mRNA expression in a dose- and time-dependent manner 24763611
Lim2405 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
LoVo Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Lim1215 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW48 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
RKO  Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW837 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW1463 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW480 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Vaco432 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Vaco400 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
DLD1 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
HT29  Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
PLC/PRF/5  Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
HepG2 Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
Hep3B  Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.021 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.029 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.033 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.047 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.049 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.051 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.063 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.094 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.108 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.114 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.114 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 0.13 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.231 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.29 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells harboring KIT T670I mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 0.38 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.522 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.549 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.833 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.834 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.943 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 1.27 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells harboring KIT D816E mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 1.35 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 2.371 μM. 30204441
GIST430 Cytotoxicity assay 72 hrs Cytotoxicity against human GIST430 cells harboring KIT V654A mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 3 μM. 28991465
BA/F3 Cytotoxicity assay 72 hrs Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 9.953 μM. 30204441
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description Regorafenib is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy.
Targets
RET [1]
(Cell-free assay)		 Raf-1 [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)		 Kit [1]
(Cell-free assay)		 VEGFR1 [1]
(Cell-free assay)		 Click to View More Targets
1.5 nM 2.5 nM 4.2 nM 7 nM 13 nM
In vitro
In vitro

Regorafenib strongly prevents VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with IC50 of 3 nM. In HAoSMCs, regorafenib suppresses PDGFR-β autophosphorylation after stimulation with PDGF-BB, with an IC50 of 90 nM. Regorafenib also inhibits FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10. Regorafenib very potently inhibited the mutant receptors KITK642E and RETC634W, with IC50 of approximately 20 nM and 10 nM, respectively. Regorafenib inhibits the proliferation of VEGF165-stimulated HUVECs, with an IC50 of approximately 3 nM. Regorafenib prevents the proliferation of FGF2-stimulated HUVECs and of PDGF-BB-stimulated HAoSMCs with IC50 of 127 nM and 146 nM, respectively. [1] Regorafenib targets both tumor cell proliferation and tumor vasculature through inhibition of receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR, and PDGFR) and serine/threonine kinases (Raf and p38MAPK). [2] Regorafenib suppresses growth of human Hep3B, PLC/PRF/5 and HepG2 cells in a concentration- and time-dependent manner. [3]
Kinase Assay Kinase assays
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. Initial in vitro kinase inhibition profiling is performed at a fixed 1 μM Regorafenib concentration. Inhibitory concentration of 50% (IC50) values are determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition is measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate.
Cell Research Cell lines GIST 882 and TT cells
Concentrations 5 nM-10 μM
Incubation Time 96 hours
Method

For proliferation assays, GIST 882 and TT cells are grown in RPMI medium containing L-glutamine, and MDA-MB-231, HepG2 and A375 cells in DMEM always containing 10% hiFBS. Cells are trypsinized, plated at 5×104 cells/well in 96-well plates in complete media containing 10% FBS and grown overnight at 37 °C. The next day, vehicle or Regorafenib serially diluted in complete growth media to between 10 μM and 5 nM final concentrations, and 0.2% DMSO, is added and incubation is continued for 96 hours. Cell proliferation is quantified.
Experimental Result Images Methods Biomarkers Images PMID
Western blot PUMA / p53 Bim / Bid / Bak / Bcl-Xl / Mcl-1 p-p65(S536) / p65 p-FGFR2 / p-FRS2α / p-AKT / p-MAPK / p-P90RSK / FGFR2 / AKT / MAPK / p90RSK Cyclin D / Cyclin E / Cyclin A / Cyclin B / p27 / p21 p-STAT3 / STAT3 / PARP / Caspase-9 24763611
Immunofluorescence p65 F-actin / Vimentin / E-cadherin 24763611
Growth inhibition assay GI50 Cell viability 29573334
In Vivo
In vivo

Regorafenib reveals potent dose-dependent TGI in various preclinical human xenograft models in mice, with tumor shrinkages in breast MDA-MB-231 and renal 786-O carcinoma models. Regorafenib prevents not only the growth of syngeneic primary 4T1 breast tumors growing orthotopically in the fat pad, but also suppresses the formation of tumor metastasis in the lung. [1]
Animal Research Animal Models Female athymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O
Dosages 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
Administration Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06321055 Not yet recruiting
Advanced Gastrointestinal Stromal Tumor
Bayer
 March 20 2024 --
NCT06137170 Active not recruiting
Metastatic Colorectal Cancer
Bayer
 March 1 2024 --
NCT06029010 Completed
Metastatic Colorectal Cancer
Bayer
 August 31 2023 --
NCT05370807 Recruiting
Melanoma Stage III|Melanoma Stage IV
Universitair Ziekenhuis Brussel
 October 3 2022 Phase 2

Chemical Information & Solubility

Molecular Weight 482.82 Formula

C21H15ClF4N4O3
CAS No. 755037-03-7 SDF Download Regorafenib SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 97 mg/mL ( (200.9 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
How to resuspend Regorafenib for in vivo studies?

Answer:
For in vivo study, we recommend to use 2% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 5mg/ml.

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