Home Protein Tyrosine Kinase VEGFR inhibitor - PDGFR inhibitor - c-Kit inhibitor - c-RET inhibitor - Raf inhibitor Regorafenib Hydrochloride

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Regorafenib Hydrochloride VEGFR inhibitor

Cat.No.S4947

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 VEGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 519.28

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Quality Control

Chemical Information, Storage & Stability

Molecular Weight 519.28 Formula

C21H16Cl2F4N4O3

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 835621-07-3 -- Storage of Stock Solutions

Synonyms Stivarga, BAY 73-4506 hydrochloride 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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (192.57 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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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. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Mechanism of Action

Targets/IC50/Ki
RET [1]
(Cell-free assay)
1.5 nM
Raf-1 [1]
(Cell-free assay)
2.5 nM
Murine VEGFR2 [1]
(Cell-free assay)
4.2 nM
Kit [1]
(Cell-free assay)
7 nM
VEGFR1 [1]
(Cell-free assay)
13 nM
PDGFRβ [1]
(Cell-free assay)
22 nM
Murine VEGFR3 [1]
(Cell-free assay)
46 nM
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.
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]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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