Cuadrado, A;
Rojo, A;
Wells, G;
Hayes, J;
Cousin, S;
Rumsey, W;
Attucks, O;
... Dinkova-Kostova, A; + view all
(2019)
Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.
Nature Reviews Drug Discovery
, 18
pp. 295-317.
10.1038/s41573-018-0008-x.
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NatRevDrugDisc2018 Cuadrado et al Keap1-Nrf2_FINAL.pdf - Accepted Version Download (1MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41573-018-0008-x |
| Publisher version: | https://doi.org/10.1038/s41573-018-0008-x |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10060781 |
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