Nrf2 activation through the inhibition of Keap1-Nrf2 protein-protein interaction
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents - 29(2020), 5 vom: 28. Mai, Seite 846-867 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Sumi [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 02.05.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1007/s00044-020-02539-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309738970 |
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| 520 | |a 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 | ||
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