Development of a cell-selective and intrinsically active multikinase inhibitor bioconjugate

Stefan Harmsen, M. Emmy M. Dolman, Zoltan Nemes, Marie Lacombe, Bálint Szokol, János Pató, György Kéri, László Öfi, Gert Storm, Wim E. Hennink, Robbert J. Kok

Research output: Contribution to journalArticle

15 Citations (Scopus)


Multikinase inhibitors are potent anticancer drugs that simultaneously intervene in multiple related signaling cascades, thus being capable of blocking salvage pathways that may play a role in the development of drug resistance. Multikinase inhibitors are increasingly evaluated for indications other than cancer, but long-term safety risks dictated by off-organ toxicities of these agents may prevent their safe and effective use. Here, we describe a new approach in which platinum coordination chemistry is applied for the development of a cell-selective multikinase inhibitor bioconjugate. The platinum(II) kinase inhibitor bioconjugate was designed to be active with the linker attached to the inhibitor and displayed improved activity by enhanced cell specificity as well as enhanced intracellular retention, thereby prolonging its pharmacological activity. In addition, the utilized platinum-based linkage technology potentiated the inhibitory activity of the multikinase inhibitor. These features in combination with carrier-mediated uptake in the target cells may revolutionize dosing regimens and safety profiles of (multi)kinase inhibitors.

Original languageEnglish
Pages (from-to)540-545
Number of pages6
JournalBioconjugate Chemistry
Issue number4
Publication statusPublished - Apr 20 2011

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Harmsen, S., Dolman, M. E. M., Nemes, Z., Lacombe, M., Szokol, B., Pató, J., Kéri, G., Öfi, L., Storm, G., Hennink, W. E., & Kok, R. J. (2011). Development of a cell-selective and intrinsically active multikinase inhibitor bioconjugate. Bioconjugate Chemistry, 22(4), 540-545.