科研之友
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摘要
Angiogenesis is a key and rate-limiting process for malignant tumor growth. Antiangiogenic agents targeting the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR-2) axis have demonstrated activity in different cancers; however, resistance develops due to the upregulation of other proangiogenic axes (fibroblast growth factor receptor [FGFR]/platelet-derived growth factor receptor [PDGFR] families). Dovitinib lactate is a small-molecule multikinase inhibitor that targets not only several proangiogenic axes, but some oncogenic kinases driving malignancies such as gastrointestinal stromal tumors (GIST), acute myeloid leukemia (AML) or bladder carcinoma. This dual effect was evidenced by potent growth inhibition of both highly angiogenesis-dependent tumors and oncogenic kinase-driven tumors in preclinical mouse models. Dovitinib lactate is administered orally, it has a t(max) of approximately 4 hours, a high volume of distribution and a long terminal half-life, and administration on a 5-days-on/2-days-off schedule resulted in manageable toxicity (mainly gastrointestinal and transaminitis) and no accumulation. Promising preliminary activity was observed in liver and kidney cancer, as well as myeloma and AML.
- 出版日期2013-2
