Investigational New Drugs

, Volume 27, Issue 4, pp 338–346 | Cite as

Screening of amide analogues of Trichostatin A in cultures of primary rat hepatocytes: search for potent and safe HDAC inhibitors

  • Joanna Fraczek
  • Sarah Deleu
  • Aneta Lukaszuk
  • Tatyana Doktorova
  • Dirk Tourwé
  • Albert Geerts
  • Tamara Vanhaecke
  • Karin Vanderkerken
  • Vera Rogiers
PRECLINICAL STUDIES

Summary

The vast majority of preclinical studies of HDAC inhibitors (HDAC-I) focus on the drug–target (cancer) cell interaction, whereas little attention is paid to the effects on non-target healthy cells, which could provide decisive information to eliminate potential cytotoxic compounds at a very early stage during drug development. In the current study we used cultures of primary rat hepatocytes as a read out system to select for the most potent HDAC-I in the group of structural analogues of an archetypal HDAC-I, namely Trichostatin A. This kind of approach allowed selecting compounds with high biological activity and with no apparent toxicity towards cultured hepatocytes.

Keywords

Histone deacetylase inhibitors Trichostatin A Hepatotoxicity Primary rat hepatocytes 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Joanna Fraczek
    • 1
  • Sarah Deleu
    • 2
  • Aneta Lukaszuk
    • 3
  • Tatyana Doktorova
    • 1
  • Dirk Tourwé
    • 3
  • Albert Geerts
    • 4
  • Tamara Vanhaecke
    • 1
  • Karin Vanderkerken
    • 2
  • Vera Rogiers
    • 1
  1. 1.Department of ToxicologyVrije Universiteit BrusselBrusselsBelgium
  2. 2.Department of Hematology and ImmunologyVrije Universiteit Brussel (VUB)BrusselsBelgium
  3. 3.Department of Organic ChemistryVrije Universiteit Brussel (VUB)BrusselsBelgium
  4. 4.Department of Cell BiologyVrije Universiteit Brussel (VUB)BrusselsBelgium

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