Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
Add to list
  1. Search results
  2. The notorious Z.B.G. : synthesis and ...

The notorious Z.B.G. : synthesis and biological evaluation of potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc-binding group to overcome therapeutic limitations

Silke Geurs (UGent)
(2022) 17th Belgian Organic Synthesis Symposium, Abstracts.
Author
Organization
Abstract
Histone deacetylase 6 (HDAC6) is a crucial regulator in various cancer types and several non-oncological conditions such as inflammation and neurodegenerative disorders. Currently, hydroxamic acid-based HDAC inhibitors are used in oncology, but their application in other therapeutic areas is hampered because of their non-selective mode of action and the potential mutagenicity associated with the hydroxamic acid zinc-binding group. To enable HDAC inhibition as a therapeutic strategy beyond oncology, we searched for a potent zinc-binding group able to replace the contested hydroxamic acid by employing a lean inhibitor strategy. The resulting, more desirable metal chelator was incorporated in a set of HDAC6-selective inhibitors. Biological evaluation of these new compounds showed an IC50 in the nanomolar range, dose-dependent HDAC6 inhibition in MM1.S cells and improved genotoxicity results, rendering these new antagonists potential hits for the non-oncologic therapeutic application of HDAC inhibitors, such as in a neurological disease context.
Keywords
HDAC, HDAC6, hydroxamic acid, mercaptoacetamide, inhibitors, oncology, neurology

Citation

Please use this url to cite or link to this publication:

MLA
Geurs, Silke. “The Notorious Z.B.G. : Synthesis and Biological Evaluation of Potent HDAC6 Selective Inhibitors with a Non-Hydroxamic Acid Zinc-Binding Group to Overcome Therapeutic Limitations.” 17th Belgian Organic Synthesis Symposium, Abstracts, 2022.
APA
Geurs, S. (2022). The notorious Z.B.G. : synthesis and biological evaluation of potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc-binding group to overcome therapeutic limitations. 17th Belgian Organic Synthesis Symposium, Abstracts. Presented at the 17th Belgian Organic Synthesis Symposium (BOSS XVII), Namur, Belgium.
Chicago author-date
Geurs, Silke. 2022. “The Notorious Z.B.G. : Synthesis and Biological Evaluation of Potent HDAC6 Selective Inhibitors with a Non-Hydroxamic Acid Zinc-Binding Group to Overcome Therapeutic Limitations.” In 17th Belgian Organic Synthesis Symposium, Abstracts.
Chicago author-date (all authors)
Geurs, Silke. 2022. “The Notorious Z.B.G. : Synthesis and Biological Evaluation of Potent HDAC6 Selective Inhibitors with a Non-Hydroxamic Acid Zinc-Binding Group to Overcome Therapeutic Limitations.” In 17th Belgian Organic Synthesis Symposium, Abstracts.
Vancouver
1.
Geurs S. The notorious Z.B.G. : synthesis and biological evaluation of potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc-binding group to overcome therapeutic limitations. In: 17th Belgian Organic Synthesis Symposium, Abstracts. 2022.
IEEE
[1]
S. Geurs, “The notorious Z.B.G. : synthesis and biological evaluation of potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc-binding group to overcome therapeutic limitations,” in 17th Belgian Organic Synthesis Symposium, Abstracts, Namur, Belgium, 2022.
@inproceedings{8761511,
  abstract     = {{Histone deacetylase 6 (HDAC6) is a crucial regulator in various cancer types and several non-oncological conditions such as inflammation and neurodegenerative disorders. Currently, hydroxamic acid-based HDAC inhibitors are used in oncology, but their application in other therapeutic areas is hampered because of their non-selective mode of action and the potential mutagenicity associated with the hydroxamic acid zinc-binding group. To enable HDAC inhibition as a therapeutic strategy beyond oncology, we searched for a potent zinc-binding group able to replace the contested hydroxamic acid by employing a lean inhibitor strategy. The resulting, more desirable metal chelator was incorporated in a set of HDAC6-selective inhibitors. Biological evaluation of these new compounds showed an IC50 in the nanomolar range, dose-dependent HDAC6 inhibition in MM1.S cells and improved genotoxicity results, rendering these new antagonists potential hits for the non-oncologic therapeutic application of HDAC inhibitors, such as in a neurological disease context.}},
  author       = {{Geurs, Silke}},
  booktitle    = {{17th Belgian Organic Synthesis Symposium, Abstracts}},
  keywords     = {{HDAC,HDAC6,hydroxamic acid,mercaptoacetamide,inhibitors,oncology,neurology}},
  language     = {{eng}},
  location     = {{Namur, Belgium}},
  title        = {{The notorious Z.B.G. : synthesis and biological evaluation of potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc-binding group to overcome therapeutic limitations}},
  year         = {{2022}},
}