2. Academic Validation
  3. Targeted Protein Degradation of Histone Deacetylases by Hydrophobically Tagged Inhibitors

Targeted Protein Degradation of Histone Deacetylases by Hydrophobically Tagged Inhibitors

  • ACS Med Chem Lett. 2023 Nov 15;14(12):1863-1868. doi: 10.1021/acsmedchemlett.3c00468.
Felix Feller 1,  Finn K Hansen 1
Affiliations

Affiliation

  • 1 Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
PMID: 38116436 DOI: 10.1021/acsmedchemlett.3c00468
Abstract

There is a growing interest in alternative strategies for targeted protein degradation. In this work, we present the development of histone deacetylase (HDAC) degraders based on hydrophobic tagging technology. To this end, a library of hydrophobically tagged HDAC inhibitors was synthesized via efficient solid-phase protocols utilizing pre-loaded resins. The subsequent biological evaluation led to the identification of our best degrader, 1a, which significantly decreased HDAC1 levels in MM.1S multiple myeloma cells.

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