PMID- 36628798
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230308
IS  - 1873-3735 (Electronic)
IS  - 0165-6147 (Linking)
VI  - 44
IP  - 3
DP  - 2023 Mar
TI  - Advances and challenges in therapeutic targeting of NRF2.
PG  - 137-149
LID - S0165-6147(22)00277-2 [pii]
LID - 10.1016/j.tips.2022.12.003 [doi]
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.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Dinkova-Kostova, Albena T
AU  - Dinkova-Kostova AT
AD  - Division of Cellular and Systems Medicine, School of Medicine, University of 
      Dundee, Dundee, DD1 9SY, UK; Department of Pharmacology and Molecular Sciences 
      and Department of Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, MD, USA. Electronic address: a.dinkovakostova@dundee.ac.uk.
FAU - Copple, Ian M
AU  - Copple IM
AD  - Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & 
      Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK. Electronic 
      address: ian.copple@liverpool.ac.uk.
LA  - eng
GR  - MR/W023806/1/Medical Research Council/United Kingdom
GR  - MR/T014644/1/Medical Research Council/United Kingdom
GR  - BB/T508111/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/X00029X/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - MR/X007413/1/Medical Research Council/United Kingdom
GR  - BB/X002780/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230109
PL  - England
TA  - Trends Pharmacol Sci
JT  - Trends in pharmacological sciences
JID - 7906158
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Humans
MH  - Drug Development
MH  - Inflammation/drug therapy
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - *NF-E2-Related Factor 2/metabolism
MH  - *Oxidative Stress/drug effects
MH  - *Molecular Targeted Therapy
OTO - NOTNLM
OT  - KEAP1
OT  - NRF2
OT  - chronic disease
OT  - electrophile
OT  - inflammation
OT  - oxidative stress
COIS- Declaration of interests A.T.D.K. is a member of the Scientific Advisory Board of 
      Evgen Pharma, and collaborates with GlaxoSmithKline and Reata Pharmaceuticals. 
      I.M.C. collaborates with AstraZeneca, Evgen Pharma, GlaxoSmithKline, and Merck & 
      Co, and provides consultancy services to Korro Bio.
EDAT- 2023/01/12 06:00
MHDA- 2023/02/25 06:00
CRDT- 2023/01/11 04:27
PHST- 2022/12/05 00:00 [received]
PHST- 2022/12/19 00:00 [revised]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/01/12 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2023/01/11 04:27 [entrez]
AID - S0165-6147(22)00277-2 [pii]
AID - 10.1016/j.tips.2022.12.003 [doi]
PST - ppublish
SO  - Trends Pharmacol Sci. 2023 Mar;44(3):137-149. doi: 10.1016/j.tips.2022.12.003. 
      Epub 2023 Jan 9.