Protein kinase inhibitor-induced endothelial cell cytotoxicity and its prediction based on calculated molecular descriptors

Eszter Herczenik, Zoltán Varga, Dániel Eors, Veronika Makó, Melinda Oroszlán, Szabolcs Rugonfalvi-Kiss, László Romics, George Füst, György Kéri, László Orfi, László Cervenak

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Protein kinase inhibitors (PKIs) as potent signal transduction therapeutic compounds represent a very rapidly expanding group of anticancer drugs. These agents may be toxic for endothelial cells, however, very few experimental data exist on the cytotoxicity of PKIs. The aim of this study was to set up an appropriate test system for endothelial cells and to assess the structure-related cytotoxic effects of a selected library of PKIs. The inhibitor library contains several lead molecules with different basic structures and a set of modified derivatives of the lead compounds. The toxicity of PKIs did not correlate directly with the structural features of the molecules. However, we successfully built up a model based on 15 calculated molecular descriptors, which is capable of predicting cytotoxicity with acceptable probability. Our results show that the cytotoxic effects of PKIs should be taken into account for optimal drug development to overcome endothelial cell-related side effects.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalJournal of Receptors and Signal Transduction
Issue number2
StatePublished - 2009
Externally publishedYes

Bibliographical note

Funding Information:
Financial support was provided by the following grants: The Hungarian National Research and Development Grants (NKFP) 1/047/2001 and 1/A/005/2004 (GF, LC, GK, LO); the ATHERNET (QLG1-CT-2002-90393) grant of European Community (GF, LC); Cooperative Research Centre Grant (KKK-01/2001, MO); GVOP-3.1.1.-2004-05-0368/3.0 (GK, LO); INCA-018704 (GK, LO); and NKFP1-010/2005 (GK, LO).


  • Cytotoxicity
  • Endothelial cells
  • Molecular descriptor
  • Protein kinase inhibitor


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