SU11657
SU11657 (N,N-Dimethyl sunitinib) is an orally active multi-targeted tyrosine kinase inhibitor with IC50 values of 0.04 μM (c-Kit), 0.005 μM (PDGFR), 0.013 μM (VEGFR1), 0.017 μM (VEGFR2) and 50 nM (FLT3), respectively. SU11657 exhibits anti-angiogenic activity. SU11657 delays leukemia progression, synergizes with ATRA (HY-14649) to reduce leukemia burden, and inhibits symptoms and tissue damage associated with rheumatoid arthritis. SU11657 can be used in research related to FLT3-mutated acute promyelocytic leukemia, rheumatoid arthritis, neuroblastoma, and benign/atypical meningioma.
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- No. CAS: 326914-17-4
- Fòrmula: C20H23FN4O2
- Peso molecular:370.43
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Almacenamiento:
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Actividad biológica
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Actividad biológica
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VEGFR1 0.013 μM (IC50) |
VEGFR2 0.017 μM (IC50) |
c-Kit 0.04 μM (IC50) |
PDGFR 0.005 μM (IC50) |
FLT3 50 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| 3T3 | IC50 |
0.1 μM
Compound: 12e
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Inhibition of Platelet-derived growth factor induced 3T3 cell proliferation
Inhibition of Platelet-derived growth factor induced 3T3 cell proliferation
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[PMID: 12646019] |
| K562 | EC50 |
12.55 μM
Compound: 20
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Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 32334266] |
| K562 | EC50 |
13.03 μM
Compound: 20
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Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 48 hrs by celltox-green assay
Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 48 hrs by celltox-green assay
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[PMID: 32334266] |
| NIH3T3 | IC50 |
0.015 μM
Compound: 12e
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Inhibition of PDGF-induced BrdU incorporation in 3T3 cells
Inhibition of PDGF-induced BrdU incorporation in 3T3 cells
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[PMID: 12646019] |
| NIH3T3 | IC50 |
0.05 μM
Compound: 12e
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Inhibition of Vascular endothelial growth factor receptor in 3T3 cells
Inhibition of Vascular endothelial growth factor receptor in 3T3 cells
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[PMID: 12646019] |
SU11657 (5-500 nM; 2 h) potently inhibits the autophosphorylation of FLT3-ITD in MV 4;11 leukemia cells, with an IC50 of approximately 50 nM[1].
SU11657 potently inhibits the kinase activities of purified VEGF-RI, VEGF-RII, PDGF-R and c-Kit proteins in vitro, with the strongest inhibitory activity against PDGF-R (IC50 = 0.005 μM) and the weakest inhibitory activity against c-Kit (IC50 = 0.04 μM)[2].
SU11657 (0-5.0 μM; 72 h) potently inhibits the proliferation of primary HUVECs, primary atypical meningioma cells and primary benign meningioma cells in a 72-hour experiment, with the strongest inhibitory activity against HUVECs (IC50 = 0.2 μM), followed by that against atypical meningioma cells (IC50 = 0.5 μM), and the weakest activity against benign meningioma cells (IC50 = 1.6-1.75 μM)[4].
SU11657 (0-5.0 μM; 14-21 days) reduces the clonogenic survival rate of primary benign meningioma cells and primary atypical meningioma cells in a dose-dependent manner, with a significantly stronger effect on atypical meningioma cells[4].
SU11657 (100 nM-1 μM) significantly enhances the inhibitory effect of radiation on the clonogenic survival of primary benign meningioma cells and primary atypical meningioma cells, with a more prominent synergistic effect observed in atypical meningioma cells[4].
SU11657 reduces HUVEC invasion induced by primary benign meningioma cells and primary atypical meningioma cells, and also attenuates the radiation-induced enhancement of this proangiogenic paracrine effect[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human MV 4;11 leukemia cell line (expresses FLT3-ITD mutation)
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Concentration:5-500 nM
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Incubation Time:2 h
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Result:Dose-dependently inhibited the autophosphorylation of FLT3-ITD in MV 4;11 cells, with an IC50 of approximately 50 nM.
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Cell Line:primary benign (endotheliomatous, transitional, fibroblastic) meningioma cells, primary atypical meningioma cells, human umbilical vein endothelial cells (HUVEC)
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Concentration:0-5.0 μM
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Incubation Time:72 h
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Result:Reduced cell number/proliferation in a dose-dependent manner across all tested cell types, with varying potencies.
Achieved an IC50 of 0.2 μM for HUVEC, an IC50 of 0.5 μM for atypical meningioma cells, an IC50 of 1.6 μM for endotheliomatous and transitional benign meningioma cells, and an IC50 of 1.75 μM for fibroblastic benign meningioma cells.
SU11657 (40 mg/kg; p.o.; daily) almost completely suppresses clinical signs of arthritis and reduces histological joint damage to near-normal levels in K/BxN transgenic mice with rheumatoid arthritis[2].
SU11657 (40 mg/kg; p.o.; daily; 10-40 days) potently inhibits subcutaneous human neuroblastoma xenograft growth and angiogenesis in nude mice via increased tumor cell apoptosis and suppressed receptor tyrosine kinase signaling, with no observed toxicity[3].
SU11657 potently inhibits tumor growth and angiogenesis in mouse models of experimental neuroblastoma[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:FVB/N mice (sublethally irradiated, injected with 1×106 activated FLT3/PML-RARα leukemic cells)[1]
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Dosage:20 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Reduced mean spleen weight from 637 mg to 403 mg and mean liver weight from 2593 mg to 1950 mg.
Caused a small increase in CD11b expression and loss of the Ly-6G-positive leukemic population in splenic cells.
Had minimal morphologic effects on bone marrow, spleen, and liver.
When combined with ATRA, reduced mean spleen weight to 90 mg and mean liver weight to 1373 mg.
Eliminated 99% of leukemic cells from the spleen, reducing GFP-positive leukocytes from 71% to 5%.
Reduced GFP-positive cells in blood and bone marrow.
Restored normal heterogeneous hematopoiesis in bone marrow, normal splenic architecture, and eliminated leukemia from the liver.
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Animal Model:KRN/NOD (K/BxN) F1 transgenic (male KRN mice with B10BR background crossed with female NOD/Orl Ico mice)[2]
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Dosage:40 mg/kg
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Administration:p.o.; daily; from 5 days before expected arthritis onset until 15 days after onset
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Result:Almost completely abrogated all clinical signs of arthritis.
Reduced mean arthritic index significantly lower than placebo-treated mice at all time points (p < 0.05).
Reduced mean histological score to 3.1 (p < 0.001 vs placebo score of 50).
Reduced cartilage proteoglycan degradation by 90%.
Reduced number of CD31-positive cells by 34% compared with placebo-treated mice.
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Animal Model:NMRI nu-nu nude mice (male, 6-7 weeks old, subcutaneous xenograft of human neuroblastoma cells, randomized when tumors reached 0.3 mL volume)[3]
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Dosage:40 mg/kg
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Administration:p.o.; daily; 10 days (SK-N-AS); 18 days (SH-SY5Y); 20 days (IMR-32); 40 days (all cell lines)
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Result:Reduced tumor volume by 90% (SK-N-AS, 10 days), 88% (SH-SY5Y, 18 days), and 93.8% (IMR-32, 20 days) compared to controls.
Increased tumor volume by 24% (SK-N-AS), 4.6% (SH-SY5Y), and 83% (IMR-32) relative to end of initial short-term treatment after 40 days of treatment, while remaining drastically smaller than controls.
Reduced vascular parameters (vessel number per grid, vessel length per tumor volume, vessel volume per tumor volume, vessel surface area per tumor volume) by 63-96% across all cell lines after short-term treatment.
Reduced vessel volume per tumor volume by 86.3% (SK-N-AS, 10 days), vessel length per tumor volume by 80.0% (SH-SY5Y, 18 days), and vessel number per grid by 89.5% (IMR-32, 20 days) after short-term treatment.
Further reduced some vascular parameters significantly in SK-N-AS and IMR-32 after long-term 40-day treatment.
Increased tumor cell apoptosis by 83% (SK-N-AS, 10 days), 40% (SH-SY5Y, 18 days), and 25% (IMR-32, 20 days) compared to controls.
Further increased tumor cell apoptosis in all cell lines after 40 days of treatment.
Increased tyrosine hydroxylase (TH)-positive cell fraction by 193% (SK-N-AS, 10 days) and 173% (SH-SY5Y, 18 days).
Reduced plasma VEGF-A concentrations significantly compared to controls at end of short-term treatment, with further reductions after 40 days.
Increased plasma concentrations of PDGF-BB and SCF per milliliter of tumor volume after short-term treatment, which decreased after 40 days.
Decreased tumor cell and endothelial cell expression of VEGFR-2, PDGFR-β, and (where present) c-KIT during therapy.
Chemical Information
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No. CAS 326914-17-4
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Peso molecular 370.43
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Fòrmula C20H23FN4O2
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SMILES
C(=C\1/C=2C(NC1=O)=CC=C(F)C2)\C3=C(C)C(C(NCCN(C)C)=O)=C(C)N3
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Synonyms
N,N-Dimethyl sunitinib
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Sohal J, et al. A model of APL with FLT3 mutation is responsive to retinoic acid and a receptor tyrosine kinase inhibitor, SU11657. Blood. 2003 Apr 15;101(8):3188-97. [Content Brief]
[2]. De Bandt M, et al. Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis. Journal of immunology (Baltimore, Md. : 1950). 2003 Nov 01;171(9):4853-9. [Content Brief]
[3]. Bäckman U, et al. The selective class III/V receptor tyrosine kinase inhibitor SU11657 inhibits tumor growth and angiogenesis in experimental neuroblastomas grown in mice. Pediatric research. 2005 May;57(5 Pt 1):690-5. [Content Brief]
[4]. Milker-Zabel S, et al. SU11657 enhances radiosensitivity of human meningioma cells. International journal of radiation oncology, biology, physics. 2008 Mar 15;70(4):1213-8. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SU11657 Related Classifications
HY-138032 Related Classifications
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