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

Regorafenib Hydrochloride

Synonyms: Stivarga, BAY 73-4506 hydrochloride

Regorafenib (Stivarga, BAY 73-4506) Hydrochloride is a multi-target inhibitor for VEGFR1, Murine VEGFR2/3, 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, respectively.

Regorafenib Hydrochloride Chemical Structure

Regorafenib Hydrochloride Chemical Structure

CAS No. 835621-07-3

Purity & Quality Control

Regorafenib Hydrochloride Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Biological Activity

Description Regorafenib (Stivarga, BAY 73-4506) Hydrochloride is a multi-target inhibitor for VEGFR1, Murine VEGFR2/3, 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, respectively.
Targets
RET [1]
(Cell-free assay)		 Raf-1 [1]
(Cell-free assay)		 Murine 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 5-10 μM
Incubation Time 96 h
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.
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 o.g.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03386825 Completed
Colorectal Neoplasms
Bayer
 January 31 2018 --
NCT01959269 Completed
Colorectal Neoplasm
Bayer
 October 31 2013 --
NCT01002378 Completed
Dietary Fats|Pharmacokinetics
Bayer
 October 2009 Phase 1
NCT01003015 Completed
Carcinoma Hepatocellular
Bayer
 September 2009 Phase 2

Chemical Information & Solubility

Molecular Weight 519.28 Formula

C21H16Cl2F4N4O3
CAS No. 835621-07-3 SDF --
Smiles Cl.CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)F
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (192.57 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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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.

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