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Regorafenib (BAY-734506) Monohydrate VEGFR inhibitor

Name: Regorafenib (BAY-734506) Monohydrate
Brand: Selleck Chemicals
SKU: S5077
Rating: 5 (50 reviews)

Cat. No.: S5077

Regorafenib (BAY-734506, Fluoro-sorafenib, Resihance, Stivarga, regorafaenib monohydrate) Monohydrate is a novel oral multikinase inhibitor with IC50 values of 13, 4.2, 46, 22, 7, 1.5, 2.5, 28, 19 nM for VEGFR1, murine VEGFR2, murine VEGFR3, PDGFR-β, Kit (c-Kit), RET (c-RET), RAF-1, B-RAF and B-RAF(V600E) respectively.

Regorafenib (BAY-734506) Monohydrate VEGFR inhibitor Chemical Structure

Estructura química

Peso molecular: 500.83

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.99%

99.99

Dianas relacionadas	EGFR FGFR PDGFR c-Met Src MEK CSF-1R HER2 FLT3 c-Kit
Otros VEGFR Inhibidores	SAR131675 SU 5402 Cediranib (AZD2171) Vatalanib (PTK787) 2HCl Anlotinib (AL3818) Dihydrochloride Linifanib (ABT-869) Apatinib (YN968D1) Apatinib (YN968D1) mesylate Ki8751 Semaxanib (SU5416)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
GISTT1	Cytotoxicity assay	72 hrs	Cytotoxicity against human GISTT1 cells assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50=0.13μM	28991465
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=0.38μM	28991465
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=1.35μM	28991465
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=3μM	28991465
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
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
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
BA/F3	Function 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=0.021μM	30204441
BA/F3	Function 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=0.029μM	30204441
BA/F3	Function 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=0.033μM	30204441
BA/F3	Function 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=0.047μM	30204441
BA/F3	Function 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=0.049μM	30204441
BA/F3	Function 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=0.051μM	30204441
BA/F3	Function 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=0.063μM	30204441
BA/F3	Function 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=0.094μM	30204441
BA/F3	Function 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=0.108μM	30204441
BA/F3	Function 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=0.114μM	30204441
BA/F3	Function 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=0.114μM	30204441
BA/F3	Function 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=0.231μM	30204441
BA/F3	Function 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=0.29μM	30204441
BA/F3	Function 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=0.522μM	30204441
BA/F3	Function 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=0.549μM	30204441
BA/F3	Function 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=0.833μM	30204441
BA/F3	Function 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=0.834μM	30204441
BA/F3	Function 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=0.943μM	30204441
BA/F3	Function 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=1.27μM	30204441
BA/F3	Function 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=2.371μM	30204441
BA/F3	Cytotoxicity assay	72 hrs	Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50=9.953μM	30204441
Sf9	Function 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, IC50=0.005μM	31284081
Sf9	Function assay	4 hrs	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 lumine, IC50=0.082μM	31721578
Sf9	Function assay	150 mins	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 , IC50=0.116μM	31721578
GISTT1	Antiproliferative assay	72 hrs	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, GI50=0.119μM	31721578
GIST882	Antiproliferative assay	144 hrs	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, GI50=0.285μM	31721578
GIST48	Antiproliferative assay	120 hrs	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, GI50=0.785μM	31721578
Caco-2	Toxicity assay	48 hrs	Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50=0.97μM	ChEMBL
Caco-2	Function assay	48 hrs	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50=1.67μM	ChEMBL
VERO-E6	Toxicity assay	48 hrs	Toxicity CC50 against VERO-E6 cells determined at 48 hours by high content imaging (same conditions as 2_LEY without exposure to 0.01 MOI SARS CoV-2 virus), CC50=8.31μM	ChEMBL
VERO-E6	Function assay	48 hrs	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging, IC50=24.95μM	ChEMBL
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	500.83	Fórmula	C₂₁H₁₅ClF₄N₄O₃.H₂O	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1019206-88-2	--		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	Fluoro-sorafenib, Resihance, Stivarga, regorafaenib monohydrate			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.O

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (199.66 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	5mg/ml (9.98mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	0.71mg/ml (1.42mM)	Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	PDGFRβ (Cell-free) RET (Cell-free) 1.5 nM Raf-1 (Cell-free) 2.5 nM murine VEGFR2 (Cell-free) 4.2 nM KIT (Cell-free) 7 nM VEGFR1 (Cell-free) 13 nM B-Raf (V600E) (Cell-free) 19 nM PDGFRβ (Cell-free) 22 nM B-Raf (Cell-free) 28 nM murine VEGFR3 (Cell-free) 46 nM
In vitro	Regorafenib strongly prevents VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with IC50 of 3 nM. In HAoSMCs, regorafenib suppress 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 KIT^K642E and RET^C634W, 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. 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). Regorafenib suppresses growth of human Hep3B, PLC/PRF/5 and HepG2 cells in a concentration- and time-dependent manner.
Ensayo de quinasa	Ensayos de quinasas
Ensayo de quinasa	Se realizan ensayos in vitro utilizando dominios quinasa recombinantes de VEGFR2 (murina aa785-aa1367), VEGFR3 (murina aa818-aa1363), PDGFRβ (aa561-aa1106), Raf-1 (aa305-aa648) y BRafV600E (aa409-aa765). El perfilado inicial de inhibición de quinasas in vitro se realiza a una concentración fija de 1 μM de Regorafenib. Los valores de concentración inhibitoria del 50 % (IC50) se determinan a partir de quinasas respondedoras seleccionadas, por ejemplo, VEGFR1 y RET. La inhibición de la quinasa TIE2 se mide con un ensayo de fluorescencia de resolución temporal homogénea (HTRF) utilizando una proteína de fusión recombinante de glutatión-S-transferasa, el dominio intracelular de TIE2 y el péptido biotina-Ahx-EPKDDAYPLYSDFG como sustrato.
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.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/21170960/ [2] https://pubmed.ncbi.nlm.nih.gov/21789125/ [3] https://pubmed.ncbi.nlm.nih.gov/22777740/

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT03386825	Completed	Colorectal Neoplasms	Bayer	January 31 2018	--
NCT01959269	Completed	Colorectal Neoplasm	Bayer	October 31 2013	--

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