|Systematic (IUPAC) name|
|Metabolism||Extensive hepatic metabolism (mostly CYP3A4-mediated)|
|Biological half-life||4.6 ± 1.1 h|
|Excretion||Fecal and renal|
|Molar mass||346.813 g·mol−1|
Vatalanib (INN, codenamed PTK787 or PTK/ZK) is a small molecule protein kinase inhibitor that inhibits angiogenesis. It is being studied as a possible treatment for several types of cancer, particularly cancer that is at an advanced stage or has not responded to chemotherapy. Vatalanib is orally active, that is, it is effective when taken by mouth.
Vatalanib is being developed by Bayer Schering and Novartis. It inhibits all known VEGF receptors, as well as platelet-derived growth factor receptor-beta and c-kit, but is most selective for VEGFR-2.
Vatalanib was discovered through high-throughput screening. It has been extensively investigated in Phase I, II and III clinical trials. Two large, randomized controlled Phase III trials have studied the effect of adding vatalanib to the FOLFOX chemotherapy regimen in people with metastatic colorectal cancer: CONFIRM-1, whose participants had not yet received any treatment for their cancer; and CONFIRM-2, in which participants had received first-line treatment with irinotecan and fluoropyrimidines. Vatalanib produced no significant improvement in overall survival (the primary endpoint of the studies), although it did significantly increase progression-free survival in CONFIRM-2. Both trials found that progression-free survival was improved in people with high levels of lactate dehydrogenase, an enzyme used as a marker of tissue breakdown; the reasons for and implications of this difference are still unclear.
The adverse effects of vatalanib appear similar to those of other VEGF inhibitors. In the CONFIRM trials, the most common side effects were high blood pressure, gastrointestinal upset (diarrhea, nausea, and vomiting), fatigue, and dizziness.
- Jost LM, Gschwind HP, Jalava T, et al. (November 2006). "Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients". Drug Metabolism and Disposition. 34 (11): 1817–28. doi:10.1124/dmd.106.009944. PMID 16882767.
- Mariani SM (2004). "Antiangiogenesis Cocktails -- Stirred or Shaken?: Highlights of the 9th Annual Drug Discovery Technology World Congress; August 8-13, 2004; Boston, Massachusetts". Medscape General Medicine. 6 (4): 21. PMC . PMID 15775848. Retrieved on October 29, 2008.
- Wood JM, Bold G, Buchdunger E, et al. (April 2000). "PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration". Cancer Research. 60 (8): 2178–89. PMID 10786682.
- Los M, Roodhart JM, Voest EE (April 2007). "Target practice: lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer". The Oncologist. 12 (4): 443–50. doi:10.1634/theoncologist.12-4-443. PMID 17470687.
- Scott EN, Meinhardt G, Jacques C, Laurent D, Thomas AL (March 2007). "Vatalanib: the clinical development of a tyrosine kinase inhibitor of angiogenesis in solid tumours". Expert Opin Investig Drugs. 16 (3): 367–79. doi:10.1517/13543722.214.171.1247. PMID 17302531.
- Ongoing and completed clinical trials of vatalanib at ClinicalTrials.gov (U.S. National Institutes of Health)