Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib).

Abstract

XL-184 (cabozantinib) is a novel, small-molecule, multitargeted 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.

• Authors: D W Bowles, E R Kessler, A Jimeno
• Journal: Drugs of today (Barcelona, Spain : 1998) (Drugs Today (Barc)) Vol. 47 Issue 11 Pg. 857-68 (Nov 2011) ISSN: 1699-3993 [Print] Spain
• PMID: 22146228 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2011 Prous Science, S.A.U. or its licensors. All rights reserved.

Chemical References

• Anilides
• Antineoplastic Agents
• Drugs, Investigational
• MAS1 protein, human
• Proto-Oncogene Mas
• Pyridines
• cabozantinib
• Receptor Protein-Tyrosine Kinases

Topics

• Anilides (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Clinical Trials as Topic
• Drug Interactions
• Drugs, Investigational (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Humans
• Neoplasms (drug therapy)
• Proto-Oncogene Mas
• Pyridines (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)