Issue 32, 2020
From the journal:

Chemical Communications

PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes†

Joshua P. Smalley,a   Grace E. Adams,b   Christopher J. Millard, ORCID logo c   Yun Song, ORCID logo ‡c   James K. S. Norris,a   John W. R. Schwabe,*c   Shaun Michael Cowley ORCID logo *b  and  James T. Hodgkinson ORCID logo *a  

* Corresponding authors

a Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, University Road, Leicester, UK
E-mail: JTHodgkinson@le.ac.uk

b Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK
E-mail: smc57@leicester.ac.uk

c Leicester Institute of Structural and Chemical Biology and Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK
E-mail: john.schwabe@le.ac.uk

Abstract

We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.

Graphical abstract: PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes

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Article information

DOI
https://doi.org/10.1039/D0CC01485K
Article type
Communication
Submitted
25 Feb 2020
Accepted
11 Mar 2020
First published
11 Mar 2020

Chem. Commun., 2020,56, 4476-4479

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PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes

J. P. Smalley, G. E. Adams, C. J. Millard, Y. Song, J. K. S. Norris, J. W. R. Schwabe, S. M. Cowley and J. T. Hodgkinson, Chem. Commun., 2020, 56, 4476 DOI: 10.1039/D0CC01485K

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