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Chemical Compound Review

Vatalanib     N-(4-chlorophenyl)-4- (pyridin-4...

Synonyms: Pynasunate, Vatalanib base, QCR-126, SureCN18286, Kinome_3657, ...
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Disease relevance of Vatalanib

  • Also, when early treatment with PTK/ZK and imatinib is commenced during the inflammatory phase of OAD development, it significantly attenuates the development of tracheal occlusion, suggesting that these drugs could potentially be used to treat bronchiolitis obliterans syndrome in its early phase [1].
  • This phase I/II trial evaluated the safety, pharmacokinetics and efficacy of PTK/ZK in patients with liver metastases from solid tumours [2].
  • Patients were administered oral PTK/ZK monotherapy once daily at doses of 300-1200 mg/day in 28-day cycles until unacceptable toxicity or tumour progression occurred [2].
  • Preliminary response, time to progression, and overall survival data were promising.1 Based on these encouraging results, PTK/ZK is currently in Phase III clinical trials for metastatic colorectal cancer [3].
  • The local application of PTK/ZK could be a new way to treat ischemic ocular diseases such as diabetic retinopathy in humans [4].

High impact information on Vatalanib

  • METHODS: In fully mismatched rat tracheal allografts, we used imatinib and PTK/ZK, either alone or in combination, to block PDGF and VEGF receptor protein tyrosine kinase (RTK) action, respectively [1].
  • Anti-angiogenic VEGF therapies are divided into two categories: one affecting the VEGF ligand, such as bevacizumab, and those that inhibit the VEGF receptor, such as PTK/ZK [5].
  • Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours [2].
  • Long-term therapy with PTK/ZK demonstrated predictable pharmacokinetics, was safe and feasible in patients with metastatic disease, and showed promising clinical activity [2].
  • The area under the concentration-time curve (AUC) of PTK/ZK increased between 300 and 1000 mg/day with no further increase from 1000 to 1200 mg/day; the AUC decreased by 50% between day 1 and day 15 [2].

Chemical compound and disease context of Vatalanib


Biological context of Vatalanib

  • Disposition and biotransformation of vatalanib were studied in an open-label, single-center study in patients with advanced cancer [7].
  • Without inhibiting tumor cell proliferation directly, PTK/ZK results in a significant retardation of tumor growth in a number of experimental tumor models of different tissue origin [3].

Anatomical context of Vatalanib


Associations of Vatalanib with other chemical compounds


Gene context of Vatalanib


Analytical, diagnostic and therapeutic context of Vatalanib

  • Preliminary data from phase I/II clinical trials of PTK/ZK as a monotherapy suggested a positive safety and tolerability profile, which we interpret to be a consequence of the high selectivity of the drug for a limited number of kinases [3].


  1. Role of Platelet-derived Growth Factor and Vascular Endothelial Growth Factor in Obliterative Airway Disease. Tikkanen, J.M., Hollm??n, M., Nyk??nen, A.I., Wood, J., Koskinen, P.K., Lemstr??m, K.B. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  2. Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. Mross, K., Drevs, J., Müller, M., Medinger, M., Marmé, D., Hennig, J., Morgan, B., Lebwohl, D., Masson, E., Ho, Y.Y., Günther, C., Laurent, D., Unger, C. Eur. J. Cancer (2005) [Pubmed]
  3. PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy. Hess-Stumpp, H., Haberey, M., Thierauch, K.H. Chembiochem (2005) [Pubmed]
  4. Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice. Maier, P., Unsoeld, A.S., Junker, B., Martin, G., Drevs, J., Hansen, L.L., Agostini, H.T. Graefes Arch. Clin. Exp. Ophthalmol. (2005) [Pubmed]
  5. Molecular mechanisms and targeting of colorectal cancer. Vanhoefer, U. Semin. Oncol. (2005) [Pubmed]
  6. Gateways to clinical trials. Bayes, M., Rabasseda, X., Prous, J.R. Methods and findings in experimental and clinical pharmacology (2006) [Pubmed]
  7. Metabolism and Disposition of Vatalanib (PTK787/ZK-222584) in Cancer Patients. Jost, L.M., Gschwind, H.P., Jalava, T., Wang, Y., Guenther, C., Souppart, C., Rottmann, A., Denner, K., Waldmeier, F., Gross, G., Masson, E., Laurent, D. Drug Metab. Dispos. (2006) [Pubmed]
  8. New drugs in cancer therapy, National Tumor Institute, Naples, 17-18 June 2004. Caponigro, F., Basile, M., de Rosa, V., Normanno, N. Anticancer Drugs (2005) [Pubmed]
  9. Future directions with angiogenesis inhibitors in colorectal cancer. Bilenker, J.H., Haller, D.G. Clinical colorectal cancer. (2004) [Pubmed]
  10. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Jain, R.K., Duda, D.G., Clark, J.W., Loeffler, J.S. Nature clinical practice. Oncology. (2006) [Pubmed]
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