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Chemical Structure| 1019206-88-2 Chemical Structure| 1019206-88-2

Structure of Regorafenib monohydrate
CAS No.: 1019206-88-2

Chemical Structure| 1019206-88-2

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Regorafenib (BAY 73-4506) monohydrate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC50 values of 13, 4.2, 46, 22, 7, 1.5, and 2.5 nM for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET, and Raf-1, respectively. Regorafenib monohydrate demonstrates robust antitumor and antiangiogenic activity.

Synonyms: BAY 73-4506 monohydrate; Fluoro-sorafenib; regorafaenib monohydrate

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Product Details of Regorafenib monohydrate

CAS No. :1019206-88-2
Formula : C21H17ClF4N4O4
M.W : 500.83
SMILES Code : O=C(NC)C1=NC=CC(OC2=CC=C(NC(NC3=CC=C(Cl)C(C(F)(F)F)=C3)=O)C(F)=C2)=C1.[H]O[H]
Synonyms :
BAY 73-4506 monohydrate; Fluoro-sorafenib; regorafaenib monohydrate
MDL No. :MFCD17170366
InChI Key :ZOPOQLDXFHBOIH-UHFFFAOYSA-N
Pubchem ID :24768591

Safety of Regorafenib monohydrate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Regorafenib monohydrate

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HCT116 40 µM 48 h Analyze apoptosis and Mcl-1 degradation induced by Regorafenib Oncogene. 2017 Feb 9;36(6):787-796.
SW837 40 µM 48 h Analyze apoptosis and Mcl-1 degradation induced by Regorafenib Oncogene. 2017 Feb 9;36(6):787-796.
Hep3B cells 1 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM 72 or 96 h Regorafenib inhibited the growth of Hep3B cells in a concentration- and time-dependent manner, with an IC50 of 5 μM. J Cell Physiol. 2013 Feb;228(2):292-7.
PLC/PRF/5 cells 1 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM 72 or 96 h PLC/PRF/5 cells responded similarly to Hep3B cells in their response to Regorafenib. J Cell Physiol. 2013 Feb;228(2):292-7.
HepG2 cells 1 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM 72 or 96 h HepG2 cells were more sensitive to Regorafenib, with an approximate IC50 of 1 μM. J Cell Physiol. 2013 Feb;228(2):292-7.
RIL-175 cells 1 µM 36 h To investigate the effect of Regorafenib on CXCL10 expression in RIL-175 cells, results showed that Regorafenib significantly increased CXCL10 secretion J Immunother Cancer. 2020 Nov;8(2):e001435.
HCA1 cells 1 µM 36 h To investigate the effect of Regorafenib on CXCL10 expression in HCA1 cells, results showed that Regorafenib increased CXCL10 secretion, but the effect was less pronounced compared to RIL-175 cells J Immunother Cancer. 2020 Nov;8(2):e001435.
T24R1 cells 1, 6.25, 12.5, 25, 50 µM 12, 24, 48 h Regorafenib significantly decreased the viability of T24R1 cells and inhibited their expression of stemness and EMT markers. Int J Mol Sci. 2023 Dec 18;24(24):17610.
T24R2 cells 1, 6.25, 12.5, 25, 50 µM 12, 24, 48 h Regorafenib significantly decreased the viability of T24R2 cells and inhibited their expression of stemness and EMT markers. Int J Mol Sci. 2023 Dec 18;24(24):17610.
SKMEL239 Parental (PAR) cells 2 μM 1 h Inhibition of MAPK signaling, Regorafenib suppressed MAPK signaling more potently in C3 cells compared to PAR cells. Cancer Discov. 2021 Jul;11(7):1716-1735.
PC9 cells 2 μM 1 h In the presence of the AP ligand, Regorafenib suppressed MAPK signaling more potently than in the absence of AP, indicating its stronger inhibition of dimeric BRAF(V600E). Cancer Discov. 2021 Jul;11(7):1716-1735.
PAR cells 4 μM 2 h Treatment of PAR cells with Regorafenib did not affect the Tm of BRAF(V600E), indicating no binding to monomeric BRAF(V600E). Cancer Discov. 2021 Jul;11(7):1716-1735.
C3 cells 2 μM 2 h Treatment of C3 cells with Regorafenib resulted in a shift in the Tm, indicating binding to the BRAF(V600E) dimer. Cancer Discov. 2021 Jul;11(7):1716-1735.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice HCT116 xenograft model Oral 30 mg/kg Once daily for 10 days Evaluate the antitumor effects of Regorafenib on FBW7-KO and WT tumors Oncogene. 2017 Feb 9;36(6):787-796.
NOD-scid Il2rγnull (NSG) mice Acute myeloid leukemia (AML) model Oral gavage 5 mg/kg Once daily for 1 month To evaluate the therapeutic potential of Regorafenib in the AML model. Results showed that AML cells in the periphery and spleen are sensitive to treatment, whereas those in the BM are protected. J Hematol Oncol. 2017 Oct 6;10(1):162
Mice HCC model with liver damage Oral 5, 10 or 20 mg/kg Once daily for 5 days To investigate the effect of Regorafenib combined with PD1 blockade in HCC models, results showed that combination therapy significantly increased survival and enhanced CD8 T-cell infiltration J Immunother Cancer. 2020 Nov;8(2):e001435.
Nude mice T24R1 and T24R2 xenografted tumor model Intraperitoneal injection 20 mg/kg 20 consecutive days Regorafenib significantly inhibited the growth of T24R1 and T24R2 xenografted tumors, reduced tumor proliferation and angiogenesis, and promoted tumor cell apoptosis. Int J Mol Sci. 2023 Dec 18;24(24):17610.
Nude mice WiDr or RKO xenograft models Orally 30 mg/kg Once daily for 40 or 60 days The triple combination of Regorafenib, Dabrafenib, and Trametinib significantly suppressed tumor growth without apparent toxicities. Cancer Discov. 2021 Jul;11(7):1716-1735.
Mice HT-29 tumor model Oral 30 mg/kg Once daily for 7 days To investigate the mechanism of tumor revascularization after Regorafenib withdrawal, the results showed that tumors rapidly revascularized after Regorafenib withdrawal, and TPC-EVs promoted EPC recruitment and tumor revascularization by activating the Axl pathway. J Extracell Vesicles. 2021 May;10(7):e12096

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.00mL

0.40mL

0.20mL

9.98mL

2.00mL

1.00mL

19.97mL

3.99mL

2.00mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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