Advances and challenges in therapeutic targeting of NRF2

Albena T. Dinkova-Kostova; Ian M. Copple

doi:10.1016/j.tips.2022.12.003

Advances and challenges in therapeutic targeting of NRF2

Albena T. Dinkova-Kostova (Lead / Corresponding author), Ian M. Copple (Lead / Corresponding author)

Research output: Contribution to journal › Review article › peer-review

73 Citations (Scopus)

196 Downloads (Pure)

Abstract

Activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet therapeutic needs, including neurodegenerative disorders and metabolic diseases. As the NRF2 field transitions into the clinical phase of its evolution, the need for an understanding of the factors influencing NRF2 pharmacology has never been greater. In this opinion article we describe the rationale for targeting NRF2, summarise the recent advances in drug development of NRF2 modulators, and reflect on the remaining challenges in realising the full clinical potential of NRF2 as a therapeutic target.

Original language	English
Pages (from-to)	137-149
Number of pages	13
Journal	Trends in Pharmacological Sciences
Volume	44
Issue number	3
Early online date	9 Jan 2023
DOIs	https://doi.org/10.1016/j.tips.2022.12.003
Publication status	Published - Mar 2023

Keywords

NRF2
KEAP1
electrophile
oxidative stress
inflammation
chronic disease

Access to Document

10.1016/j.tips.2022.12.003Licence: CC BY

Final Published VersionFinal published version, 2.51 MBLicence: CC BY

Cite this

@article{b63d58b61adf4b5d81b60bda3dc67875,

title = "Advances and challenges in therapeutic targeting of NRF2",

abstract = "Activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet therapeutic needs, including neurodegenerative disorders and metabolic diseases. As the NRF2 field transitions into the clinical phase of its evolution, the need for an understanding of the factors influencing NRF2 pharmacology has never been greater. In this opinion article we describe the rationale for targeting NRF2, summarise the recent advances in drug development of NRF2 modulators, and reflect on the remaining challenges in realising the full clinical potential of NRF2 as a therapeutic target.",

keywords = "NRF2, KEAP1, electrophile, oxidative stress, inflammation, chronic disease",

author = "Dinkova-Kostova, {Albena T.} and Copple, {Ian M.}",

note = "Funding Information: Research in the laboratory of A.T.D.K. is funded by the Medical Research Council (MR/W023806/1 and MR/T014644/1), the Biotechnology and Biological Sciences Research Council (BB/T508111/1 and BB/X00029X/1), Medical Research Scotland, Reata Pharmaceuticals, GSK Plc, and the Ninewells Cancer Campaign. Work in the laboratory of I.M.C. is funded by a Medical Research Council Senior Non-clinical Fellowship (MR/X007413/1) and by the Biotechnology and Biological Sciences Research Council (BB/X002780/1). This article is facilitated by collaboration through COST Action CA20121, supported by the European Cooperation in Science and Technology (www.cost.eu) (https://benbedphar.org/about-benbedphar/). Copyright: {\textcopyright} 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license. ",

year = "2023",

month = mar,

doi = "10.1016/j.tips.2022.12.003",

language = "English",

volume = "44",

pages = "137--149",

journal = "Trends in Pharmacological Sciences",

issn = "0165-6147",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Advances and challenges in therapeutic targeting of NRF2

AU - Dinkova-Kostova, Albena T.

AU - Copple, Ian M.

N1 - Funding Information: Research in the laboratory of A.T.D.K. is funded by the Medical Research Council (MR/W023806/1 and MR/T014644/1), the Biotechnology and Biological Sciences Research Council (BB/T508111/1 and BB/X00029X/1), Medical Research Scotland, Reata Pharmaceuticals, GSK Plc, and the Ninewells Cancer Campaign. Work in the laboratory of I.M.C. is funded by a Medical Research Council Senior Non-clinical Fellowship (MR/X007413/1) and by the Biotechnology and Biological Sciences Research Council (BB/X002780/1). This article is facilitated by collaboration through COST Action CA20121, supported by the European Cooperation in Science and Technology (www.cost.eu) (https://benbedphar.org/about-benbedphar/). Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license.

PY - 2023/3

Y1 - 2023/3

N2 - Activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet therapeutic needs, including neurodegenerative disorders and metabolic diseases. As the NRF2 field transitions into the clinical phase of its evolution, the need for an understanding of the factors influencing NRF2 pharmacology has never been greater. In this opinion article we describe the rationale for targeting NRF2, summarise the recent advances in drug development of NRF2 modulators, and reflect on the remaining challenges in realising the full clinical potential of NRF2 as a therapeutic target.

AB - Activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet therapeutic needs, including neurodegenerative disorders and metabolic diseases. As the NRF2 field transitions into the clinical phase of its evolution, the need for an understanding of the factors influencing NRF2 pharmacology has never been greater. In this opinion article we describe the rationale for targeting NRF2, summarise the recent advances in drug development of NRF2 modulators, and reflect on the remaining challenges in realising the full clinical potential of NRF2 as a therapeutic target.

KW - NRF2

KW - KEAP1

KW - electrophile

KW - oxidative stress

KW - inflammation

KW - chronic disease

UR - http://www.scopus.com/inward/record.url?scp=85146039329&partnerID=8YFLogxK

U2 - 10.1016/j.tips.2022.12.003

DO - 10.1016/j.tips.2022.12.003

M3 - Review article

C2 - 36628798

SN - 0165-6147

VL - 44

SP - 137

EP - 149

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

IS - 3

ER -

Advances and challenges in therapeutic targeting of NRF2

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

The Role of Nrf2 in the Tumour Microenvironment of IDH Wild-Type Glioma (Joint with University of Edinburgh)

Defining the Oxidative Stress-Related Mechanisms by which Activation of the Transcription Factor Nrf2 Arrests and Resolves Liver Fibrosis

Cite this

Advances and challenges in therapeutic targeting of NRF2

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Projects

The Role of Nrf2 in the Tumour Microenvironment of IDH Wild-Type Glioma (Joint with University of Edinburgh)

Defining the Oxidative Stress-Related Mechanisms by which Activation of the Transcription Factor Nrf2 Arrests and Resolves Liver Fibrosis

Cite this