Vatalanib

Not to be confused with Vandetanib.

Vatalanib

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Systematic (IUPAC) name
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin- 1-amine
Clinical data
Pregnancy category	None assigned
Routes of administration	Oral
Legal status
Legal status	Investigational
Pharmacokinetic data
Bioavailability	High
Metabolism	Extensive hepatic metabolism (mostly CYP3A4-mediated)
Biological half-life	4.6 ± 1.1 h
Excretion	Fecal and renal
Identifiers
CAS Number	212141-54-3
ATC code	none
PubChem	CID 151194
ChemSpider	133257
Chemical data
Formula	C20H15ClN4
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.

Development

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.

Adverse effects

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.

External links

• Ongoing and completed clinical trials of vatalanib at ClinicalTrials.gov (U.S. National Institutes of Health)