Projects per year
Abstract
The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. However, challenges regarding target specificity, pharmacodynamic properties, efficacy and safety remain.
Original language | English |
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Pages (from-to) | 295-317 |
Number of pages | 23 |
Journal | Nature Reviews Drug Discovery |
Volume | 18 |
Issue number | 4 |
Early online date | 4 Jan 2019 |
DOIs | |
Publication status | Published - Apr 2019 |
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
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Dive into the research topics of 'Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases'. Together they form a unique fingerprint.Projects
- 3 Finished
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Contribution by NRF2 Upregulation to Lung Carcinogenesis and the Possible Therapeutic Value of NRF2 Inhibition by GSK-3 (Joint with Universities of St Andrews, Edinburgh and Pennsylvania)
Dinkova-Kostova, A. (Investigator), Hayes, J. (Investigator), Henderson, C. (Investigator), Keyse, S. (Investigator), Lamond, A. (Investigator) & Sutherland, C. (Investigator)
1/05/16 → 31/10/19
Project: Research
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The Role of the Keap1/Nrf2 Pathway in Tumour Metabolic Adaptation (Joint with University of Cambridge and University College London)
Dinkova-Kostova, A. (Investigator)
1/06/15 → 30/04/21
Project: Research
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The Spatiotemporal Regulation of the Keap1/Nrf2 Pathway (Joint with University College London)
Dinkova-Kostova, A. (Investigator)
Biotechnology and Biological Sciences Research Council
30/09/14 → 27/02/18
Project: Research