PROTAC-mediated Degradation of Class I Histone Deacetylase Enzymes in Corepressor Complexes

Overview

Journal Chem Commun (Camb)

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2020 Mar 24

PMID 32201871

Citations 40

Authors

Joshua P Smalley

Grace E Adams

Christopher J Millard

Yun Song

James K S Norris

John W R Schwabe

Shaun Michael Cowley

James T Hodgkinson

Affiliations

Soon will be listed here.

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.

Citing Articles

PROTACs Targeting Epigenetic Proteins.

Zhang C, He Y, Sun X, Wei W, Liu Y, Rao Y Acta Mater Med. 2024; 2(4):409-429.

PMID: 39221114 PMC: 11364368. DOI: 10.15212/amm-2023-0039.

Degraders in epigenetic therapy: PROTACs and beyond.

Dai X, Ji S, Fu M, Liu G, Liu H, Wang S Theranostics. 2024; 14(4):1464-1499.

PMID: 38389844 PMC: 10879860. DOI: 10.7150/thno.92526.

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies.

Peng X, Hu Z, Zeng L, Zhang M, Xu C, Lu B Acta Pharm Sin B. 2024; 14(2):533-578.

PMID: 38322348 PMC: 10840439. DOI: 10.1016/j.apsb.2023.09.003.

MDM2 Antagonist Idasanutlin Reduces HDAC1/2 Abundance and Corepressor Partners but Not HDAC3.

Smalley J, Cowley S, Hodgkinson J ACS Med Chem Lett. 2024; 15(1):93-98.

PMID: 38229760 PMC: 10788946. DOI: 10.1021/acsmedchemlett.3c00449.

Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues.

Pichlak M, Sobierajski T, Blazewska K, Gendaszewska-Darmach E J Enzyme Inhib Med Chem. 2023; 38(1):2254012.

PMID: 37667522 PMC: 10481767. DOI: 10.1080/14756366.2023.2254012.

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