MULTI-TARGETED TYROSINE KINASE INHIBITORS IN CLINICAL DEVELOPMENT: FOCUS ON XL-184 (CABOZANTINIB)

作者：Bowles D W; Kessler E R; Jimeno A^*

来源：Drugs of Today, 2011, 47(11): 857-868.

DOI：10.1358/dot.2011.47.11.1688487

XL-184 (cabozantinib) is a novel, small-molecule, multi-targeted receptor tyrosine kinase inhibitor with particular activity against hepatocyte growth factor receptor (tyrosine-protein kinase Met), vascular endothelial growth factor receptor 2 (VEGFR-2) and proto-oncogene tyrosine-protein kinase receptor Ret. There is ample evidence of Met, VEGFR-2 and Ret signaling in several tumor types. Preclinical data suggest that XL-184 has activity in tumors derived from both epithelial and mesenchymal origins. Phase I and II clinical studies support significant antitumor activity, particularly in medullary thyroid cancer and cancers metastatic to the bone. This review will evaluate XL-184's preclinical pharmacology, pharmacokinetics, drug interactions and clinical activity in phase I through phase III studies.

• 出版日期2011-11