Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity

Salma Darwish
  • Function : Author
Ehab Ghazy
  • Function : Author
Tino Heimburg
  • Function : Author
Daniel Herp
  • Function : Author
Patrik Zeyen
  • Function : Author
Rabia Salem-Altintas
  • Function : Author
Johannes Ridinger
  • Function : Author
Dina Robaa
  • Function : Author
Karin Schmidtkunz
  • Function : Author
Frank Erdmann
  • Function : Author
Matthias Schmidt
  • Function : Author
Manfred Jung
  • Function : Author
Ina Oehme
  • Function : Author
Wolfgang Sippl
  • Function : Author

Abstract

In addition to involvement in epigenetic gene regulation, histone deacetylases (HDACs) regulate multiple cellular processes through mediating the activity of non-histone protein substrates. The knockdown of HDAC8 isozyme is associated with the inhibition of cell proliferation and apoptosis enhancement in several cancer cell lines. As shown in several studies, HDAC8 can be considered a potential target in the treatment of cancer forms such as childhood neuroblastoma. The present work describes the development of proteolysis targeting chimeras (PROTACs) of HDAC8 based on substituted benzhydroxamic acids previously reported as potent and selective HDAC8 inhibitors. Within this study, we investigated the HDAC8-degrading profiles of the synthesized PROTACs and their effect on the proliferation of neuroblastoma cells. The combination of in vitro screening and cellular testing demonstrated selective HDAC8 PROTACs that show anti-neuroblastoma activity in cells.
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Dates and versions

hal-04219177 , version 1 (26-09-2023)

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Salma Darwish, Ehab Ghazy, Tino Heimburg, Daniel Herp, Patrik Zeyen, et al.. Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity. International Journal of Molecular Sciences, 2022, 23 (14), ⟨10.3390/ijms23147535⟩. ⟨hal-04219177⟩
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