Small molecule targeting of chromatin writers in cancer.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
13
11
2020
accepted:
13
10
2021
pubmed:
26
12
2021
medline:
19
2
2022
entrez:
25
12
2021
Statut:
ppublish
Résumé
More than a decade after the launch of DNA methyltransferase and histone deacetylase inhibitors for the treatment of cancer, 2020 heralded the approval of the first histone methyltransferase inhibitor, revitalizing the concept that targeted manipulation of the chromatin regulatory landscape can have profound therapeutic impact. Three chromatin regulatory pathways-DNA methylation, histone acetylation and methylation-are frequently implicated in human cancer but hundreds of potentially druggable mechanisms complicate identification of key targets for therapeutic intervention. In addition to human genetics and functional screening, chemical biology approaches have proven critical for the discovery of key nodes in these pathways and in an ever-increasing complexity of molecularly defined human cancer contexts. This review introduces small molecule targeting approaches, showcases chemical probes and drug candidates for epigenetic writer enzymes, illustrates molecular features that may represent epigenetic dependencies and suggests translational strategies to maximize their impact in cancer therapy.
Identifiants
pubmed: 34952934
doi: 10.1038/s41589-021-00920-5
pii: 10.1038/s41589-021-00920-5
doi:
Substances chimiques
Antineoplastic Agents
0
Chromatin
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-133Informations de copyright
© 2021. Springer Nature America, Inc.
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