Nrf2 activation through the inhibition of Keap1-Nrf2 protein-protein interaction.
Keap1
Keap1-Nrf2 interaction
Nrf2
Oxidative stress
Protein-protein interaction Inhibitor
Structure-activity relationship
Journal
Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents
ISSN: 1054-2523
Titre abrégé: Med Chem Res
Pays: United States
ID NLM: 9211347
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
entrez:
12
5
2020
pubmed:
12
5
2020
medline:
12
5
2020
Statut:
ppublish
Résumé
Activation of the transcription factor Nrf2 via the Keap1-Nrf2-ARE signaling system regulates the transcription and subsequent expression of cellular cytoprotective proteins and plays a crucial role in preventing pathological conditions exacerbated by the overproduction of oxidative stress. In addition to electrophilic modulators, direct non-covalent inhibitors that interrupt the Keap1-Nrf2 protein-protein interaction (PPI) leading to Nrf2 activation have attracted a great deal of attention as potential preventive and therapeutic agents for oxidative stress-related diseases. Structural studies of Keap1-binding ligands, development of biochemical and cellular assays, and new structure-based design approaches have facilitated the discovery of small molecule PPI inhibitors. This perspective reviews the Keap1-Nrf2-ARE system, its physiological functions, and the recent progress in the discovery and the potential applications of direct inhibitors of Keap1-Nrf2 PPI.
Identifiants
pubmed: 32390710
doi: 10.1007/s00044-020-02539-y
pmc: PMC7207041
mid: NIHMS1583939
doi:
Types de publication
Journal Article
Langues
eng
Pagination
846-867Subventions
Organisme : NCI NIH HHS
ID : R01 CA133791
Pays : United States
Déclaration de conflit d'intérêts
Declaration of Conflicting Interests The authors have filed patents on some of the compounds discussed in this paper.
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