Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity.
Fiche publication
Date publication
juillet 2022
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Darwish S, Ghazy E, Heimburg T, Herp D, Zeyen P, Salem-Altintas R, Ridinger J, Robaa D, Schmidtkunz K, Erdmann F, Schmidt M, Romier C, Jung M, Oehme I, Sippl W
Lien Pubmed
Résumé
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.
Mots clés
HDAC8, histone deacetylases (HDACs), neuroblastoma, proteolysis targeting chimera (PROTAC), synthesis
Référence
Int J Mol Sci. 2022 07 7;23(14):