Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation

Research output: Contribution to journalArticle


A novel class of tyrosine kinase blockers represented by the tyrphostins AG1295 and AG1296 is described. These compounds inhibit selectively the platelet-derived growth factor (PDGF) receptor kinase and the PDGF-dependent DNA synthesis in Swiss 3T3 cells and in porcine aorta endothelial cells with 50% inhibitory concentrations below 5 and 1 microM, respectively. The PDGF receptor blockers have not effect on epidermal growth factor receptor autophosphorylation; weak effects on DNA synthesis stimulated by insulin, by epidermal growth factor, or by a combination of both; and over an order of magnitude weaker blocking effect on fibroblast growth factor-dependent DNA synthesis. AG1296 potently inhibits signaling of human PDGF alpha- and beta-receptors as well as of the related stem cell factor receptor (c-Kit) but has no effect on autophosphorylation of the vascular endothelial growth factor receptor KDR or on DNA synthesis induced by vascular endothelial growth factor in porcine aortic endothelial cells. Treatment by AG1296 reverses the transformed phenotype of sis-transfected NIH 3T3 cells but has no effect on src-transformed NIH 3T3 cells or on the activity of the kinase p60c-src(F527) immunoprecipitated from these cells. These potent and selective compounds represent leads for the development of novel agents to combat tumors driven by PDGF or to inhibit PDGF action in other diseases in which PDGF plays a key role, such as restenosis.


  • Marina Kovalenko
  • Aviv Gazit
  • A Böhmer
  • Charlotte Rorsman
  • Lars Rönnstrand
  • Carl-Henrik Heldin
  • Johannes Waltenberger
  • Frank D. Böhmer
  • A Levitzki
External organisations
  • External Organization - Unknown
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry


  • Epidermal Growth Factor/antagonists & inhibitors Receptors, 3T3 Cells Animals Antineoplastic Agents/*pharmacology Catechols/*pharmacology Cell Division/drug effects Cell Transformation, Neoplastic/*drug effects DNA/biosynthesis Mice Nitriles/*pharmacology Phosphorylation Platelet-Derived Growth Factor/pharmacology Proto-Oncogene Proteins Proto-Oncogene Proteins c-sis Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors Receptor, Platelet-Derived Growth Factor/*metabolism *Tyrphostins
Original languageEnglish
Pages (from-to)6106-6114
JournalCancer Research
Issue number23
Publication statusPublished - 1994
Publication categoryResearch
Externally publishedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)