Evidence map›Paper›PMID 30610225›Full record

ReviewNature reviews. Drug discovery2019

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.

Antonio Cuadrado, Ana I Rojo, Geoffrey Wells, John D Hayes, Sharon P Cousin, William L Rumsey, Otis C Attucks, Stephen Franklin, Anna-Liisa Levonen, Thomas W Kensler and 1 more

Open access · greenAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Drug discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 806 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
806citing papers in PubMed, 1 pooled it
54.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

806 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,312 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026
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  13. Review
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  15. Mechanism of Cinnamaldehyde in AlleviatingAnimals : an open access journal from MDPI · 2026
    Article
  16. International journal of molecular sciences · 2026
    Review
  17. Review
  18. Article
  19. Article
  20. Article

746 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 10 institutions in 5 countries.

Antonio CuadradoCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Department of Biochemistry and Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
Ana I RojoCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Department of Biochemistry and Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
Geoffrey WellsUCL School of Pharmacy, University College London, London, UK.ORCID http://orcid.org/0000-0002-0253-911X
John D HayesJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, Scotland, UK.
Sharon P CousinReata Pharmaceuticals, Irving, TX, USA.
William L RumseyGlaxoSmithKline, Collegeville, PA, USA.
Otis C AttucksvTv Therapeutics, High Point, NC, USA.
Stephen FranklinEvgen Pharma, Wilmslow, Cheshire, UK.
Anna-Liisa LevonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Thomas W KenslerTranslational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Albena T Dinkova-KostovaJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, Scotland, UK. a.dinkovakostova@dundee.ac.uk.ORCID http://orcid.org/0000-0003-0316-9859
Biomedical Research Networking Center on Neurodegenerative Diseases · ESEvgen Pharma (United Kingdom) · GBFred Hutch Cancer Center · USGlaxoSmithKline (United States) · USJohns Hopkins University · USReata Pharmaceuticals (United States) · USUniversity College London · GBUniversity of Dundee · GBUniversity of Eastern Finland · FIvTv Therapeutics (United States) · US

Funding

Biotechnology and Biological Sciences Research Council BB/L01923X/1Cancer Research UK 10268Cancer Research UK 18644Medical Research Council MR/N009851/1
6 · The paper itself

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.

Indexed as

Drug TherapyActivation, MetabolicAnimalsHumansKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2KEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2

Identifiers

PMID30610225
OpenAlexW2907855283

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.