SU10944
SU10944 is a selective, orally active VEGFR inhibitor, with an IC50 of 6 nM against VEGFR-1, an IC50 of 96 nM and a Ki of 21 nM against VEGFR-2. SU10944 only exhibits weak inhibitory activity against PDGFRβ (IC50 = 1 μM), SCFR (IC50 = 1.58 μM) and FGFR-1 (IC50 = 1.6 μM). SU10944 selectively inhibits VEGFR receptor downstream signaling, neovascularization, vascular permeability, VEGF-mediated tissue factor production, and induces tumor growth delay. SU10944 can be used in research related to diabetic retinopathy, exudative age-related macular degeneration or cancer.
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- CAS No.: 515821-11-1
- Formule: C17H16N2O3
- Masse moléculaire:296.33
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
Description
IC50 & Target
[1]|
VEGFR1 6 nM (IC50) |
VEGFR2 96 nM (IC50) |
FGFR1 1/6 μM (IC50) |
In Vitro
SU10944 (2 h) inhibits VEGFR-2 autophosphorylation in transiently transfected human embryonic kidney 293T cells with an IC50 of 227 nM[1].
SU10944 (0.2-25 μM; 20 h) dose-dependently inhibits VEGF-induced VEGFR-2 autophosphorylation in stably transfected NIH/3T3 cells, with maximal inhibition at 25 μM[1].
SU10944 (varying concentrations; 4 h) inhibits VEGF-induced tissue factor production in human umbilical vein endothelial cells with an IC50 of 102 nM, without affecting PMA-stimulated tissue factor production[1].
SU10944 (varying concentrations; 20 h (3T3 assays); 3 days (MO7e assay)) inhibits SCFR-dependent MO7e cell survival (IC50 = 1.6 μM) and PDGFRβ-dependent 3T3 cell proliferation (IC50 = 30.6 μM), but does not inhibit EGFR- or FGFR-1-dependent 3T3 cell proliferation (IC50 > 50 μM) and is not cytotoxic to 3T3 cells at concentrations up to 50 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:NIH/3T3 cells (stably expressing mouse VEGFR-2)
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Concentration:0.2, 1, 5 and 25 μM
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Incubation Time:20 h
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Result:Dose-dependently inhibited VEGF-induced VEGFR-2 autophosphorylation, with near-complete inhibition at 25 μM.
In Vivo
SU10944 (3-100 mg/kg; p.o.; single dose) time- and dose-dependently inhibits VEGF-induced vascular permeability in athymic mice, with a plasma concentration of 250 ng/mL correlating to 50% inhibition[1].
SU10944 (150 mg/kg; p.o.; once daily; 12 days) induces 76% growth inhibition of C6 glioma xenografts in nu/nu mice, accompanied by modest antiangiogenic activity[2].
SU10944 (150 mg/kg; p.o.; once daily; 15 days) induces 95% growth inhibition and maintains stasis of MV4;11 leukemia xenografts in nu/nu mice, with modest antiangiogenic activity[2].
SU10944 (150 mg/kg; p.o.; once daily; 18 days) induces 55% growth inhibition of HT-29 colon carcinoma xenografts in nu/nu mice[2].
SU10944 (150 mg/kg; p.o.; once daily; 14 days) induces 90% growth inhibition of 786-O renal carcinoma xenografts in nu/nu mice, accompanied by significant antiangiogenic activity[2].
SU10944 (150 mg/kg; p.o.; once daily; 29 days) induces 82% growth inhibition of WM-266-4 melanoma xenografts in nu/nu mice, with modest antiangiogenic activity[2].
SU10944 (150 mg/kg; p.o.; once daily; 14 days) induces 28% growth inhibition of H226 lung carcinoma xenografts in nu/nu mice, with moderate antiangiogenic activity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic[1]
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Dosage:3 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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Result:Inhibited VEGF-induced vascular permeability in a time- and dose-dependent manner.
Sustained maximum inhibition up to 2 hours at 100 mg/kg, with 50% inhibition still apparent 24 hours postdose.
Showed maximum inhibition at 1 hour and decreased to zero by 24 hours at 30 mg/kg.
Associated 50% inhibition of VEGF-mediated vascular permeability with a plasma concentration of 250 ng/mL (844 nM).
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, rat C6 glioma cells implanted s.c. into hindflank)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 12 days
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Result:Induced 76% tumor growth inhibition.
Reduced tumor microvessel density (MVD) by 20% relative to vehicle-treated controls.
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, human MV4;11 FLT3-ITD-mutated leukemia cells implanted s.c. into hindflank with 50% Matrigel)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 15 days
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Result:Induced 95% tumor growth inhibition.
Maintained tumor stasis.
Reduced tumor microvessel density (MVD) by 40% relative to vehicle-treated controls.
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, human HT-29 colon carcinoma cells implanted s.c. into hindflank with 50% Matrigel)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 18 days
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Result:Induced 55% tumor growth inhibition.
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, human 786-O renal carcinoma cells implanted s.c. into hindflank with 50% Matrigel)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 14 days
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Result:Induced 90% tumor growth inhibition.
Reduced tumor microvessel density (MVD) by 54% relative to vehicle-treated controls.
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, human WM-266-4 melanoma cells implanted s.c. into hindflank)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 29 days
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Result:Induced 82% tumor growth inhibition.
Reduced tumor microvessel density (MVD) by 23% relative to vehicle-treated controls.
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Animal Model:nu/nu (female, 8-12 weeks old, 25 g, human H226 lung carcinoma cells implanted s.c. into hindflank)[2]
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Dosage:150 mg/kg
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Administration:p.o.; once daily; 14 days
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Result:Induced 28% tumor growth inhibition.
Reduced tumor microvessel density (MVD) by 42% relative to vehicle-treated controls.
Chemical Information
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CAS No. 515821-11-1
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Masse moléculaire 296.33
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Formule C17H16N2O3
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SMILES
O=C(O)CCC=1C=C(NC1C=C2C(=O)NC=3C=CC=CC32)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Transepithelial/transendothelial electrical resistance assay
TEER measures electrical resistance across epithelial or endothelial monolayers cultured on permeable supports, and the readout reflects ionic conductance through the cell barrier, especially the paracellular pathway regulated by junctional integrity. TEER can be measured without destroying the monolayer and is commonly used before or during transport, permeability, barrier-disruption, and barrier-maturation experiments. TEER values are influenced by biological maturation and technical conditions; reported factors include temperature, medium formulation, passage number, electrode geometry, membrane properties, and junctional length during early monolayer maturation. Therefore, TEER should be interpreted with blank-insert subtraction, area normalization, repeated readings, and, when possible, orthogonal barrier readouts such as FITC-dextran flux or tight-junction staining.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Pureté et documentation
Références
[1]. Patel N, et al. A selective and oral small molecule inhibitor of vascular epithelial growth factor receptor (VEGFR)-2 and VEGFR-1 inhibits neovascularization and vascular permeability. J Pharmacol Exp Ther. 2003;306(3):838-845. [Content Brief]
[2]. Potapova O, et al. Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248. Mol Cancer Ther. 2006;5(5):1280-1289. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)