ArticleCell chemical biology2019
Non-covalent NRF2 Activation Confers Greater Cellular Protection than Covalent Activation.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Insight into Nrf2: a bibliometric and visual analysis from 2000 to 2022.Frontiers in genetics · 2023Pooled it
- The Discovery of GSK3227634: A Potent Inhaled Inhibitor of the KEAP1/NRF2 Protein-Protein Interaction for the Treatment of Chronic Obstructive Pulmonary Disease.Journal of medicinal chemistry · 2026Article
- Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Targeting DPP9 attenuates podocyte injury by regulating NRF2 antioxidant signaling.Frontiers in pharmacology · 2026Article
- Virtual Screening of Kelch-like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Inhibitors and In Vitro Validation.Molecules (Basel, Switzerland) · 2025Article
- Pharmacological targeting of the mitochondrial phosphatase PTPMT1 sensitizes hepatocellular carcinoma to ferroptosis.Cell death & disease · 2025Article
- Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis.World journal of surgical oncology · 2024Article
- Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting.Scientific reports · 2024Article
- A Novel Analog of the Natural Product Fraxinellone Protects against Endogenous and Exogenous Neurotoxicants.ACS chemical neuroscience · 2024Article
- The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review.Antioxidants (Basel, Switzerland) · 2023Review
- COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism.Cell death & disease · 2022Article
- COPD lung studies of Nrf2 expression and the effects of Nrf2 activators.Inflammopharmacology · 2022Article
- Activation of the Nrf2 Pathway as a Therapeutic Strategy for ALS Treatment.Molecules (Basel, Switzerland) · 2022Review
- Targeting NRF2 to treat cancer.Seminars in cancer biology · 2021Review
- The intricacies of NRF2 regulation in cancer.Seminars in cancer biology · 2021Review
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
- Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas.Frontiers in pharmacology · 2021Article
- Article
- NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway.Redox biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factor NRF2 confers cellular protection by maintaining cellular redox homeostasis and proteostasis. Basal NRF2 levels are normally low due to KEAP1-mediated ubiquitylation and subsequent proteasomal degradation. KEAP1, a substrate adaptor protein of a KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex, contains a critical cysteine (C151) that is modified by electrophiles or oxidants, resulting in inactivation of the E3 ligase and inhibition of NRF2 degradation. Currently, nearly all NRF2 inducers are electrophilic molecules that possess unwanted off-target effects due to their reactive nature. Here, we report a group of NRF2 inducers, ent-kaurane diterpenoid geopyxins, with and without C151 reactive electrophilic moieties. Among 16 geopyxins, geopyxin F, a non-electrophilic NRF2 activator, showed enhanced cellular protection relative to an electrophilic NRF2 activator, geopyxin C. To our knowledge, this is the first detailed structure-activity relationship study of covalent versus non-covalent NRF2 activators, showing the promise of non-covalent NRF2 activators as potential therapeutic compounds.
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Registered trials
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.