説明
Sunitinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) involved
in tumor proliferation and angiogenesis, including platelet-derived growth factor
receptors (PDGFR), vascular endothelial growth factor receptors (VEGFR), and
stem cell factor receptor (KIT). It was launched as an oral treatment for
gastrointestinal stromal tumors (GIST) and advanced renal-cell carcinoma (RCC).
In vitro, sunitib inhibits VEGFR2, PDGFRα, PDGFRβ, KIT, and FLT3 receptors
with IC50 values in the 4–14nM range, and the ligand-dependent autophosphorylation
of VEGFR2 and PDGFRb with IC50s of approximately 10 nM.
In addition, it inhibits the growth of tumor cells expressing dysregulated target RTKs in vitro and inhibits PDGFRb- and VEGFR2-dependent tumor angiogenesis
in vivo. Sunitinib exhibits broad and potent antitumor activity, causing regression
in murine models of human epidermal (A431), colon (Colo205 and HT-29), lung
(NCI-H226 and H460), breast (MDA-MB-435), prostate (PC3-3M-luc), and renal
(786-O) cancers, and suppressing or delaying the growth of many others,
including the C6 rat and SF763 T human glioma xenografts and B16 melanoma
lung cancer.
