Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor.

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Roskoski R Jr

Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor.

Biochem Biophys Res Commun. 2007 May 4;356(2):323-8. Epub 2007 Mar 7.

PubMed ID

17367763 [ View in PubMed

]

Abstract

Sunitinib (SU-11248, Sutent) inhibits at least eight receptor protein-tyrosine kinases including vascular endothelial growth factor receptors 1-3 (VEGFR1-VEGFR3), platelet-derived growth factor receptors (PDGFRalpha and PDGFRbeta), stem cell factor receptor (Kit), Flt-3, and colony-stimulating factor-1 receptor (CSF-1R). VEGFR1 and VEGFR2 play key roles in vasculogenesis and angiogenesis. PDGFRbeta, which is found in pericytes that surround capillary endothelial cells, plays a pivotal role in stabilizing the vascular endothelium. Sunitinib inhibits angiogenesis by diminishing signaling through VEGFR1, VEGFR2, and PDGFRbeta. Renal cell cancers that have metastasized, or spread from the primary tumor, exhibit extensive vascularity, and sunitinib is approved for the treatment of these neoplasms. Activating Kit mutations occur in about 85% of gastrointestinal stromal tumors and activating PDGFRalpha mutations occur in about 5% of these tumors. Sunitinib is approved for the treatment of those tumors that are resistant to imatinib (STI-571, Gleevec), another Kit and PDGFRalpha protein-tyrosine kinase inhibitor. Both sunitinib and imatinib bind reversibly to the ATP binding site of their target kinases and thereby inhibit their catalytic activity.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sunitinib	Macrophage colony-stimulating factor 1 receptor	Protein	Humans	Yes	Inhibitor	Details
Sunitinib	Mast/stem cell growth factor receptor Kit	Protein	Humans	Yes	Inhibitor	Details
Sunitinib	Vascular endothelial growth factor receptor 1	Protein	Humans	Yes	Inhibitor	Details
Sunitinib	Vascular endothelial growth factor receptor 3	Protein	Humans	Yes	Inhibitor	Details