PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes.
Animals
Humans
Mice
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Cell Survival
/ drug effects
Co-Repressor Proteins
/ metabolism
Histone Deacetylase 1
/ antagonists & inhibitors
Histone Deacetylase Inhibitors
/ chemistry
Histone Deacetylases
/ metabolism
Histone Demethylases
/ antagonists & inhibitors
Proteolysis
Journal
Chemical communications (Cambridge, England)
ISSN: 1364-548X
Titre abrégé: Chem Commun (Camb)
Pays: England
ID NLM: 9610838
Informations de publication
Date de publication:
21 Apr 2020
21 Apr 2020
Historique:
pubmed:
24
3
2020
medline:
29
12
2020
entrez:
24
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32201871
doi: 10.1039/d0cc01485k
pmc: PMC7610821
mid: EMS124169
doi:
Substances chimiques
Antineoplastic Agents
0
Co-Repressor Proteins
0
HDAC1 protein, human
EC 3.5.1.98
Histone Deacetylase 1
EC 3.5.1.98
Histone Deacetylase Inhibitors
0
Histone Deacetylases
EC 3.5.1.98
Histone Demethylases
EC 1.14.11.-
KDM1A protein, human
EC 1.5.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4476-4479Subventions
Organisme : Wellcome Trust
ID : 100237
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_18054
Pays : United Kingdom
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