Reactivos e instrumentos para inmunología, biología celular y biología molecular.

Regorafenib [755037-03-7]

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Referencia HY-10331-1mL

embalaje : 10mM/1mL

Marca : MedChemExpress

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Descripciòn

Regorafenib (BAY 73-4506) 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 VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib shows very robust antitumor and antiangiogenic activity^[1].

IC₅₀ & Target^[1]

Raf-1

2.5 nM (IC₅₀)

Tie2

311 ± 46 nM (IC₅₀)

VEGFR2

4.2 nM (IC₅₀)

VEGFR1

13 nM (IC₅₀)

BRaf^V600E

19 nM (IC₅₀)

PDGFRβ

22 nM (IC₅₀)

Braf

28 nM (IC₅₀)

VEGFR3

46 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	CC₅₀	14.15 μM Compound: 26	Cytotoxicity against human A549 cells Cytotoxicity against human A549 cells	[PMID: 33539089]
A549	EC₅₀	> 1000 nM Compound: Regorafenib	Antiproliferative activity against human A549 cells after 72 hrs by MTT assay Antiproliferative activity against human A549 cells after 72 hrs by MTT assay	[PMID: 27010810]
A549	IC₅₀	2.05 μM Compound: Regorafenib	Antiproliferative activity against human A549 cells after 48 hrs by MTT assay Antiproliferative activity against human A549 cells after 48 hrs by MTT assay	[PMID: 31158755]
BaF3	GI₅₀	9.953 μM Compound: 3	Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay	[PMID: 30204441]
BaF3	IC₅₀	3.89 nM Compound: Regorafenib	Antiproliferative activity against VEGFR2-transformed mouse BaF3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antiproliferative activity against VEGFR2-transformed mouse BaF3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
Caco-2	CC₅₀	0.97 μM Compound: REGORAFENIB	Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay	10.21203/rs.3.rs-23951/v1
Caco-2	IC₅₀	1.67 μM Compound: REGORAFENIB	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging	10.21203/rs.3.rs-23951/v1
GIST430	GI₅₀	3000 nM Compound: 3	Cytotoxicity against human GIST430 cells harboring KIT V654A mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay Cytotoxicity against human GIST430 cells harboring KIT V654A mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay	[PMID: 28991465]
GIST430	GI₅₀	> 2000 nM Compound: 3	Antiproliferative activity against human GIST430 cells harboring c-KIT exon 11 primary in-frame V560-L576 deletion mutant and exon 13 heterozygous secondary missense V654A mutant assessed as cell growth inhibition after 120 hrs by methylene blue staining based assay Antiproliferative activity against human GIST430 cells harboring c-KIT exon 11 primary in-frame V560-L576 deletion mutant and exon 13 heterozygous secondary missense V654A mutant assessed as cell growth inhibition after 120 hrs by methylene blue staining based assay	[PMID: 31721578]
GIST48	GI₅₀	785 nM Compound: 3	Antiproliferative activity against human GIST48 cells harboring c-KIT exon 11 homozygous primary missense V560D mutant and exon 17 heterozygous secondary D820A mutant assessed as cell growth inhibition after 120 hrs by methylene blue staining based assay Antiproliferative activity against human GIST48 cells harboring c-KIT exon 11 homozygous primary missense V560D mutant and exon 17 heterozygous secondary D820A mutant assessed as cell growth inhibition after 120 hrs by methylene blue staining based assay	[PMID: 31721578]
GIST882	GI₅₀	285 nM Compound: 3	Antiproliferative activity against human GIST882 cells harboring c-KIT exon 13 homozygous primary K642E mutant assessed as cell growth inhibition after 144 hrs by methylene blue staining based assay Antiproliferative activity against human GIST882 cells harboring c-KIT exon 13 homozygous primary K642E mutant assessed as cell growth inhibition after 144 hrs by methylene blue staining based assay	[PMID: 31721578]
GISTT1	GI₅₀	119 nM Compound: 3	Antiproliferative activity against human GISTT1 cells harboring heterozygous deletion mutation at C-kit exon 11 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human GISTT1 cells harboring heterozygous deletion mutation at C-kit exon 11 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
GISTT1	GI₅₀	130 nM Compound: 3	Cytotoxicity against human GISTT1 cells assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay Cytotoxicity against human GISTT1 cells assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay	[PMID: 28991465]
GISTT1	GI₅₀	1350 nM Compound: 3	Cytotoxicity against human GISTT1 cells harboring KIT D816E mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay Cytotoxicity against human GISTT1 cells harboring KIT D816E mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay	[PMID: 28991465]
GISTT1	GI₅₀	380 nM Compound: 3	Cytotoxicity against human GISTT1 cells harboring KIT T670I mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay Cytotoxicity against human GISTT1 cells harboring KIT T670I mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay	[PMID: 28991465]
HCT-116	IC₅₀	0.16 μM Compound: Regorafenib	Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay	[PMID: 31158755]
HCT-116	IC₅₀	1.36 μM Compound: Regorafenib	Antitumor activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
HCT-116	IC₅₀	3.5 μM Compound: Regorafenib	Cytotoxicity against human HCT-116 cells assessed as cell growth inhibition by MTT assay Cytotoxicity against human HCT-116 cells assessed as cell growth inhibition by MTT assay	[PMID: 35763868]
HT-29	EC₅₀	> 1000 nM Compound: Regorafenib	Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay	[PMID: 27010810]
HT-29	IC₅₀	2.87 μM Compound: Regorafenib	Anticancer activity against human HT-29 cells assessed as inhibition of cell proliferation by MTT assay Anticancer activity against human HT-29 cells assessed as inhibition of cell proliferation by MTT assay	[PMID: 32731184]
HT-29	IC₅₀	4.21 μM Compound: Regorafenib	Antitumor activity against human HT-29 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human HT-29 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
HT-29	IC₅₀	8.6 μM Compound: Regorafenib	Cytotoxicity against human HT-29 cells assessed as cell growth inhibition by MTT assay Cytotoxicity against human HT-29 cells assessed as cell growth inhibition by MTT assay	[PMID: 35763868]
HUVEC	IC₅₀	4.21 nM Compound: Regorafenib	Antiproliferative activity against VEGF-stimulated HUVEC assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antiproliferative activity against VEGF-stimulated HUVEC assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
HeLa	IC₅₀	2.66 μM Compound: Regorafenib	Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay	[PMID: 31158755]
HepG2	IC₅₀	10.43 μM Compound: Reg	Antiproliferative activity against human HepG2 cells measured after 48 hrs by MTT assay Antiproliferative activity against human HepG2 cells measured after 48 hrs by MTT assay	[PMID: 35434624]
HepG2	IC₅₀	4.06 μM Compound: Regorafenib	Antiproliferative activity against human HepG2 cells after 48 hrs by MTT assay Antiproliferative activity against human HepG2 cells after 48 hrs by MTT assay	[PMID: 31158755]
MCF7	IC₅₀	2.71 μM Compound: Regorafenib	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay	[PMID: 31158755]
MDA-MB-231	IC₅₀	1.21 μM Compound: Regorafenib	Antitumor activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
MDA-MB-468	IC₅₀	3.02 μM Compound: Regorafenib	Antitumor activity against human MDA-MB-468 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human MDA-MB-468 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
MGC-803	IC₅₀	9.46 μM Compound: Reg	Antiproliferative activity against human MGC-803 cells measured after 48 hrs by MTT assay Antiproliferative activity against human MGC-803 cells measured after 48 hrs by MTT assay	[PMID: 35434624]
MOLM-13	GI₅₀	887 nM Compound: 3	Antiproliferative activity against human MOLM13 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human MOLM13 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
NCM460	IC₅₀	198.16 μM Compound: Regorafenib	Cytotoxicity against human NCM460 cells assessed as reduction in cell viability after 48 hrs by MTT assay Cytotoxicity against human NCM460 cells assessed as reduction in cell viability after 48 hrs by MTT assay	[PMID: 31158755]
OVCAR-3	IC₅₀	3.4 μM Compound: Regorafenib	Antitumor activity against human OVCAR-3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human OVCAR-3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
SK-OV-3	IC₅₀	3.85 μM Compound: Regorafenib	Antitumor activity against human SK-OV-3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay Antitumor activity against human SK-OV-3 cells assessed as inhibition of cell proliferation incubated for 3 days by MTT assay	[PMID: 37429211]
SW-620	IC₅₀	1.17 μM Compound: Regorafenib	Antiproliferative activity against human SW620 cells after 48 hrs by MTT assay Antiproliferative activity against human SW620 cells after 48 hrs by MTT assay	[PMID: 31158755]
Sf9	IC₅₀	0.005 μM Compound: II; BAY 73-450	Inhibition of human N-terminal GST tagged VEGFR-2 expressed in baculovirus infected Sf9 cells using poly (Glu,Tyr) 4:1 as substrate in presence of ATP by Kinase-Glo luminescence assay Inhibition of human N-terminal GST tagged VEGFR-2 expressed in baculovirus infected Sf9 cells using poly (Glu,Tyr) 4:1 as substrate in presence of ATP by Kinase-Glo luminescence assay	[PMID: 31284081]
Sf9	IC₅₀	116 nM Compound: 3	Inhibition of recombinant N-terminal 6x-His-tagged c-KIT (547 to 935 residues)/(694 to 753 residues deletion) (unknown origin) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate measured after 150 mins in presence of ATP by ADP-glo reagent based luminescence assay Inhibition of recombinant N-terminal 6x-His-tagged c-KIT (547 to 935 residues)/(694 to 753 residues deletion) (unknown origin) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate measured after 150 mins in presence of ATP by ADP-glo reagent based luminescence assay	[PMID: 31721578]
Sf9	IC₅₀	82 nM Compound: 3	Inhibition of wild type recombinant GST-tagged FLT3 (Y567 to S993 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using Her2 peptide as substrate measured after 4 hrs in presence of ATP by Kinase-Glo Plus reagent-based luminescence assay Inhibition of wild type recombinant GST-tagged FLT3 (Y567 to S993 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using Her2 peptide as substrate measured after 4 hrs in presence of ATP by Kinase-Glo Plus reagent-based luminescence assay	[PMID: 31721578]
T-24	IC₅₀	5.98 μM Compound: Reg	Antiproliferative activity against human T24 cells measured after 48 hrs by MTT assay Antiproliferative activity against human T24 cells measured after 48 hrs by MTT assay	[PMID: 35434624]

In Vitro

Regorafenib (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells^[1].
Regorafenib (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2^[1].
Regorafenib causes a concentration-dependent decrease in Hep3B cell growth, with an IC₅₀ of 5 μM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay^[1]

Cell Line:	GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells
Concentration:	10 μM and 5 nM
Incubation Time:	96 h
Result:	Showed anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells, with IC₅₀ values of 45 ± 20, 34 ± 8, 401 ± 88, 560 ± 200, 900, 967 ± 287 nM. respectively.

Western Blot Analysis^[1]

Cell Line:	NIH-3T3/VEGFR2 cells, (CHO)-TIE2 cells, HAoSMCs cells, MCF-7 cells
Concentration:	0, 10, 30, 100, 300, 1000, 3000 nM
Incubation Time:	30 min
Result:	Inhibited the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, with IC₅₀ values of 3, 31, and 90 nM, respectively, inhibited FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10, and showed inhibition of phosphorylated FGFR substrate 2 (pFRS2) and the downstream signaling kinase pERK1/2.

In Vivo

Regorafenib (10 mg/kg, Orally, single dose or daily for 4 days) inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model^[1].
Regorafenib (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Rat GS9L glioblastoma xenograft^[1]
Dosage:	10 mg/kg
Administration:	Orally, single dose or daily for 4 days
Result:	Inhibited tumor vasculature and tumor growth in a rat GS9L glioblastoma model.

Animal Model:	Female athymic NCr nu/nu mice, Multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors^[1]
Dosage:	0, 3, 10, 30, 100 mg/kg
Administration:	Orally, qd × 9
Result:	Effectively inhibited growth of the Colo-205, MDA-MB-231 and 786-O model. Significantly reduces tumor MVA, effectively inhibited the RAF/MEK/ERK signaling cascade, and drastically inhibited tumor cell proliferation.

Ensayo clínico

Peso molecular

482.82

Fòrmula

C₂₁H₁₅ClF₄N₄O₃

No. CAS

755037-03-7

Appearance

Solid

Color

White to off-white

SMILES

O=C(NC1=CC=C(C(C(F)(F)F)=C1)Cl)NC2=CC=C(OC3=CC(C(NC)=O)=NC=C3)C=C2F

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvente y solubilidad

In Vitro:

DMSO : 125 mg/mL (258.90 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0712 mL	10.3558 mL	20.7117 mL
5 mM	0.4142 mL	2.0712 mL	4.1423 mL
10 mM	0.2071 mL	1.0356 mL	2.0712 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 7.5 mg/mL (15.53 mM); Clear solution

This protocol yields a clear solution of ≥ 7.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (75.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 2

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: 2.75 mg/mL (5.70 mM); Suspended solution; Need ultrasonic
Protocol 3

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.18 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.

Pureza y Documentación

Purity: 99.93%

Ficha de datos (278 KB) SDS (393 KB)

COA (245 KB) LCMS (86 KB) Elemental Analysis Report (102 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Wilhelm SM, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 2011, 129(1), 245-255. [Content Brief]

[2]. Heng DY, et al. Targeted therapy for metastatic renal cell carcinoma: current treatment and future directions. Ther Adv Med Oncol, 2010, 2(1), 39-49. [Content Brief]

[3]. Carr BI, et al. Fluoro-Bay 43-9006 (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery. J Cell Physiol, 2013, 228(2), 292-297. [Content Brief]

[4]. Wagner J, et al. Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly impacts colorectal cancer growth and survival in vivo through complementary non-overlapping mechanisms. J Exp Clin Cancer Res. 2018 Jan 22;37(1):11. [Content Brief]

[5]. Matsuoka K, et al. Effective Sequential Combined Chemotherapy with Tipiracil and Regorafenib in Human Colorectal Cancer Cells. Int J Mol Sci. 2018 Sep 25;19(10). pii: E2915. [Content Brief]

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Regorafenib [755037-03-7]

Referencia HY-10331-1mL

Marca : MedChemExpress

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