Discovery of histone deacetylase 3 (HDAC3)-specific PROTACs.
Benzamides
/ chemistry
Catalytic Domain
Cell Line, Tumor
Cell Proliferation
/ drug effects
Histone Deacetylase Inhibitors
/ chemistry
Histone Deacetylases
/ chemistry
Humans
Proteasome Endopeptidase Complex
/ metabolism
Proteolysis
/ drug effects
Ubiquitin
/ metabolism
Ubiquitin-Protein Ligases
/ metabolism
Journal
Chemical communications (Cambridge, England)
ISSN: 1364-548X
Titre abrégé: Chem Commun (Camb)
Pays: England
ID NLM: 9610838
Informations de publication
Date de publication:
25 Aug 2020
25 Aug 2020
Historique:
entrez:
26
8
2020
pubmed:
26
8
2020
medline:
17
4
2021
Statut:
ppublish
Résumé
Histone deacetylases (HDACs) are validated drug targets for cancer treatment. Increased HDAC isozyme selectivity and novel strategies to inhibit HDAC activity could lead to safer and more effective drug candidates. Nonetheless, it is quite challenging to develop isozyme-specific HDACi due to the highly conserved catalytic domain. We discovered XZ9002, a first-in-class HDAC3-specific PROTAC that potently degraded HDAC3. Importantly, XZ9002 is more effective to inhibit cancer cell proliferation than its proteolysis-inactive counterpart, suggesting HDAC3 degradation is a novel and promising anticancer approach.
Identifiants
pubmed: 32840532
doi: 10.1039/d0cc03243c
pmc: PMC7654701
mid: NIHMS1615674
doi:
Substances chimiques
Benzamides
0
Histone Deacetylase Inhibitors
0
Ubiquitin
0
benzamide
6X80438640
Ubiquitin-Protein Ligases
EC 2.3.2.27
Proteasome Endopeptidase Complex
EC 3.4.25.1
Histone Deacetylases
EC 3.5.1.98
histone deacetylase 3
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9866-9869Subventions
Organisme : NIH HHS
ID : S10 OD021758
Pays : United States
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