Design, synthesis and biological characterization of histone deacetylase 8 (HDAC8) proteolysis targeting chimeras (PROTACs) with anti-neuroblastoma activity
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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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International journal of molecular sciences. - 23, 14 (2022) , 7535, ISSN: 1422-0067
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
-
Universität
- (when)
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2022
- Creator
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Darwish, Salma
Ghazy, Ehab Mohamed Elbassiony
Heimburg, Tino
Herp, Daniel
Zeyen, Patrik
Salem-Altintas, Rabia
Ridinger, Johannes
Robaa, Dina
Schmidtkunz, Karin
Erdmann, Frank
Schmidt, Matthias R.
Romier, Christophe
Jung, Manfred
Oehme, Ina
Sippl, Wolfgang
- DOI
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10.3390/ijms23147535
- URN
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urn:nbn:de:bsz:25-freidok-2300248
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:22 AM CEST
Data provider
This object is provided by:
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Darwish, Salma
- Ghazy, Ehab Mohamed Elbassiony
- Heimburg, Tino
- Herp, Daniel
- Zeyen, Patrik
- Salem-Altintas, Rabia
- Ridinger, Johannes
- Robaa, Dina
- Schmidtkunz, Karin
- Erdmann, Frank
- Schmidt, Matthias R.
- Romier, Christophe
- Jung, Manfred
- Oehme, Ina
- Sippl, Wolfgang
- Universität
Time of origin
- 2022
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Proteolysis targeting chimeras (PROTACs) for epigenetics research
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HaloTag‐targeted sirtuin‐rearranging ligand (SirReal) for the development of proteolysis‐targeting chimeras (PROTACs) against the lysine deacetylase sirtuin 2 (Sirt2)
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Proteolysis targeting chimeras (PROTACs) for epigenetics research
HaloTag‐Targeted Sirtuin‐Rearranging Ligand (SirReal) for the Development of Proteolysis‐Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2) **
HaloTag‐targeted sirtuin‐rearranging ligand (SirReal) for the development of proteolysis‐targeting chimeras (PROTACs) against the lysine deacetylase sirtuin 2 (Sirt2)
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Synthese und Untersuchung von peptidischen Substraten der Histondeacetylasen
Molecular Modelling Untersuchungen zum Bindungsverhalten von Histamin H2- und H3-Rezeptor-Liganden
Epigenetic drug discovery
Klinische Erfahrungen mit N1-n-Butylbiguanid in der Behandlung des Diabetes mellitus
Compton-Effekt am Proton im Bereich der ersten Resonanz : (Messung differentieller Wirkungsquerschnitte)
Aromatic amino acid hydroxylases as off-targets of histone deacetylase inhibitors
Epigenetic targets in drug discovery
Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke schistosoma mansoni
Proteolysis targeting chimeras (PROTACs) for epigenetics research
HaloTag‐Targeted Sirtuin‐Rearranging Ligand (SirReal) for the Development of Proteolysis‐Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2) **
HaloTag‐targeted sirtuin‐rearranging ligand (SirReal) for the development of proteolysis‐targeting chimeras (PROTACs) against the lysine deacetylase sirtuin 2 (Sirt2)
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Synthese und Untersuchung von peptidischen Substraten der Histondeacetylasen
Molecular Modelling Untersuchungen zum Bindungsverhalten von Histamin H2- und H3-Rezeptor-Liganden
Epigenetic drug discovery
Klinische Erfahrungen mit N1-n-Butylbiguanid in der Behandlung des Diabetes mellitus
Compton-Effekt am Proton im Bereich der ersten Resonanz : (Messung differentieller Wirkungsquerschnitte)
Aromatic amino acid hydroxylases as off-targets of histone deacetylase inhibitors
Epigenetic targets in drug discovery