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.