Sunitinib |
Katalog-Nr.GC17651
One-Click Copy Product Info
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Sunitinib (SU 11248) ist ein Multi-Targeting-Rezeptor-Tyrosinkinase-Inhibitor mit IC50-Werten von 80 nM bzw. 2 nM fÜr VEGFR2 und PDGFRβ. Sunitinib, ein ATP-kompetitiver Inhibitor, hemmt wirksam die Autophosphorylierung von Ire1α, indem es die Autophosphorylierung und die daraus resultierende RNase-Aktivierung hemmt.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 557795-19-4
Sample solution is provided at 25 µL, 10mM.
Sunitinib (SU 11248) is an orally active multi-target receptor tyrosine kinase inhibitor with IC50 values of 80 nM and 2 nM for vascular endothelial growth factor receptor (VEGFR2) and platelet-derived growth factor receptor (PDGFRβ), respectively[1]. Sunitinib is an ATP-competitive inhibitor that effectively inhibits the phosphorylation of Ire1α by inhibiting autophosphorylation and subsequent RNase activation[2]. Sunitinib is commonly used to treat advanced renal cell carcinoma and gastrointestinal stromal cancer, as well as non-small cell lung cancer[3].
In vitro, treatment of renal cancer cell 786-O with Sunitinib (2, 5 μM) induced changes in the intracellular phosphorylated proteome, with 180 phosphopeptides showing >1.5-fold changes, 86 phosphopeptides downregulated, and 94 phosphopeptides upregulated[4]. Sunitinib (0-5μM) treatment of medulloblastoma VC312 cells for 24h or 48h increased the levels of cleaved caspase-3 and PARP in a dose-dependent manner, induced cell apoptosis, and inhibited STAT3 and AKT activity[5].
In vivo, oral treatment of mice inoculated with 4T1-luc and RENCA-luc tumor cells with Sunitinib (30, 60, 120mg/kg) failed to inhibit the growth of 4T1 tumors after mouse lung implantation, but significantly inhibited the growth of RENCA tumors[6]. Sunitinib (1mg/kg) treatment of diabetic rats for 4 weeks significantly reduced ovarian stromal degeneration, stromal fibrosis, follicular degeneration, and immune expression of NF-kappaB[7].
References:
[1] Sun L, Liang C, Shirazian S, et al. Discovery of 5-[5-fluoro-2-oxo-1, 2-dihydroindol-(3 Z)-ylidenemethyl]-2, 4-dimethyl-1 H-pyrrole-3-carboxylic acid (2-diethylaminoethyl) amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase[J]. Journal of medicinal chemistry, 2003, 46(7): 1116-1119.
[2] Ali M M U, Bagratuni T, Davenport E L, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response[J]. The EMBO journal, 2011, 30(5): 894-905.
[3] Gridelli C, Maione P, Del Gaizo F, et al. Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer[J]. The oncologist, 2007, 12(2): 191-200.
[4] Van Der Mijn J C, Broxterman H J, Knol J C, et al. Sunitinib activates Axl signaling in renal cell cancer[J]. International journal of cancer, 2016, 138(12): 3002-3010.
[5] Yang F, Jove V, Xin H, et al. Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways[J]. Molecular Cancer Research, 2010, 8(1): 35-45.
[6] Welti J C, Powles T, Foo S, et al. Contrasting effects of sunitinib within in vivo models of metastasis[J]. Angiogenesis, 2012, 15: 623-641.
[7] Erbas O, Pala H G, Pala E E, et al. Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study[J]. Gynecological Endocrinology, 2015, 31(5): 388-391.
| Cell experiment [1]: | |
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Cell lines |
786-O cells |
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Preparation Method |
Phosphoproteome analysis was performed on lysates of 786-O cells that were untreated or exposed to 2 and 5 μM sunitinib for 2 h. Treatment with 1.0 μM staurosporine was used as a positive control for inhibition of tyrosine kinases. |
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Reaction Conditions |
2、5μM; 2h |
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Applications |
At both sunitinib concentrations, 180 phosphopeptides from 129 proteins showed >1.5-fold changes in more than 2 out of 3 experiments. Of these, 86 phosphopeptides were downregulated and 94 were upregulated. |
| Animal experiment [2]: | |
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Animal models |
Female Balb/c mice |
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Preparation Method |
Female Balb/c mice were injected intravenously with 4T1-luc or RENCA-luc tumor cells. Drugs (30, 60, or 120 mg/kg/day sunitinib) were given by oral gavage for 7 days. |
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Dosage form |
30, 60, 120 mg/kg/day; p.o. |
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Applications |
Sunitinib fails to inhibit the growth of 4T1 tumours after they have seeded in the lungs of mice, sunitinib can significantly suppress the growth of RENCA tumours. |
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References: [1] Van Der Mijn J C, Broxterman H J, Knol J C, et al. Sunitinib activates Axl signaling in renal cell cancer[J]. International journal of cancer, 2016, 138(12): 3002-3010. [2] Welti J C, Powles T, Foo S, et al. Contrasting effects of sunitinib within in vivo models of metastasis[J]. Angiogenesis, 2012, 15: 623-641. |
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| Cas No. | 557795-19-4 | SDF | |
| Chemical Name | N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide | ||
| Canonical SMILES | CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C | ||
| Formula | C22H27FN4O2 | M.Wt | 398.47 |
| Löslichkeit | 19.9mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5096 mL | 12.548 mL | 25.096 mL |
| 5 mM | 501.9 μL | 2.5096 mL | 5.0192 mL |
| 10 mM | 251 μL | 1.2548 mL | 2.5096 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)