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Sunitinib malate

Catalog No.
A8255
VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$55.00
In stock
Evaluation Sample
$28.00
In stock
100mg
$50.00
In stock
500mg
$100.00
In stock
1g
$150.00
In stock
2g
$200.00
In stock

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Email: [email protected]

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Background

Sunitinib malate, also called sunitinib, is a novel, oral, multi-targeted , small molecule oxindole tyrosine kinase inhibitor which inhibits multiple receptor tyrosine kinases including platelet-derived growth factor receptor ( and (, vascular endothelial growth factor receptor 1, 2 and 3, c-KIT, FLT3 kinase, colony-stimulating factor 1 receptor and RET kinase [2][3] [4]. The IC50 of sunitinib is approximately 10-20 ng/ml to NB cell lines, which is within the clinically relevant human trough serum concentration (50-100 ng/ml) [1].

Receptor tyrosine kinases activated a number of different intracellular signaling pathways [5].

In neuroblastoma (NB) cell lines, SKN-BE (2), NUB-7, SH-SY5Y and LAN-5, sunitinib significantly inhibited cell proliferation after a treatment for 48 hours, in a concentration-dependent manner [1].

Treatment with 20, 30 or 40 mg/kg of sunitinib made NOD/SCID mice inoculated with xenograft tumor cells show significant reduction (P

References:
[1].  Libo Zhang, Kristen M. Smith, Amy Lee Chong, et al. In Vivo Antitumor and Antimetastatic Activity of Sunitinib in Preclinical Neuroblastoma Mouse Model. Neoplasia, 2009, 11: 426-435.
[2].  Hassane Izzedine, Irina Buhaescu, Olivier Rixe, et al. Sunitinib malate. Cancer Chemother Pharmacol, 2007, 60: 357-364.
[3].  M. L. Telli, R. M. Witteles, G. A. Fisher, et al. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Annals of Oncology, 2008, 19: 1613–1618.
[4].  Edwin P. Rock, Vicki Goodman, Janet X. Jiang, et al. Food and Drug Administration Drug Approval Summary: Sunitinib Malate for the Treatment of Gastrointestinal Stromal Tumor and Advanced Renal Cell Carcinoma. The Oncologist, 2007, 12: 107-113.
[5].  C. J. Marshall. Specificity of Receptor Tyrosine Kinase Signaling: Transient versus Sustained Extracellular Signal-Regulated Kinase Activation. Cel, 1995, 80: 179-185.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at 4°C
M.Wt532.56
Cas No.341031-54-7
FormulaC22H27FN4O2·C4H6O5
SynonymsSU 11248,SU11248,SU-11248,Sunitinib
Solubility≥26.65mg/mL in DMSO,insoluble in EtOH, ≥4.6 mg/mL in H2O with ultrasonic
Chemical NameN-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide;(2S)-2-hydroxybutanedioic acid
SDFDownload SDF
Canonical SMILESCCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C.C(C(C(=O)O)O)C(=O)O
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

NIH-3T3 cells, HUVECs

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Applications

In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibited VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation. Sunitinib inhibited VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibited PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively.

Animal experiment [1]:

Animal models

Tumor xenograft mouse models bearing HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435 cells

Dosage form

Oral dosing, 20-80 mg/kg/day, once daily

Application

Sunitinib (20-80 mg/kg/day) exhibited broad and potent dose-dependent anti-tumor activity against a variety of tumor xenograft models including HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435. Sunitinib (80 mg/kg/day for 21 days) led to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Sunitinib treatment significantly decreased tumor MVD, with ~40% reduction in SF763T glioma tumors. SU11248 completely inhibited additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Mendel D B, Laird A D, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors[J]. Clinical Cancer Research, 2003, 9(1): 327-337.

Biological Activity

Description Sunitinib Malate is a multi-targeted inhibitor of RTK for VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM.
Targets VEGFR2 (Flk-1) PDGFRβ        
IC50 80 nM 2 nM        

Quality Control