ArticleThe Journal of biological chemistry2015
Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- An ML-Based QSAR Web Server for KEAP1 Inhibitor Bioactivity Prediction: Composite-Score-Driven Training and Advanced Validation.ACS omega · 2026Article
- Isolation of Secondary Metabolites fromPlants (Basel, Switzerland) · 2026Article
- Ligustrazine attenuates high-fat diet-induced neurobehavioral deficits and hepatic dysfunction via modulation of the HO-1/Nrf-2/SIRT-1/PPAR-α axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Phytochemical, in silico, and in vitro studies of wheatgrass (Triticum aestivum L.) juice powder.Scientific reports · 2026Article
- Heteroleptic Metal Complexes of 4-(2-Pyridylazo)resorcinol and 1,10-Phenanthroline: Synthesis, Comprehensive Characterization, Electrochemical and Antioxidant Properties, and Computational Investigations.Bioinorganic chemistry and applications · 2026Article
- A Dynamic DNA Nano-Antioxidant Targeting Galectin-3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel 2-oxopyrrolidine derivative (LN-53) efficiently induces Nrf-2 signaling pathway activation in human epidermal keratinocytes.Pharmacological reports : PR · 2025Article
- A Novel Analog of the Natural Product Fraxinellone Protects against Endogenous and Exogenous Neurotoxicants.ACS chemical neuroscience · 2024Article
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- The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?Antioxidants (Basel, Switzerland) · 2024Review
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- KEAP1-NRF2 protein-protein interaction inhibitors: Design, pharmacological properties and therapeutic potential.Medicinal research reviews · 2023Review
- Ameliorative effect of two structurally divergent hydrazide derivatives against DSS-induced colitis by targeting Nrf2 and NF-κB signaling in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein-Protein Interaction Inhibitors with an Alternative Binding Mode.Journal of medicinal chemistry · 2022Article
- Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein-Protein Interactions: An Update.Antioxidants (Basel, Switzerland) · 2022Review
- A bioactive ligand-conjugated iridium(III) metal-based complex as a Keap1-Nrf2 protein-protein interaction inhibitor against acetaminophen-induced acute liver injury.Redox biology · 2021Article
- Purification, Identification and Characterization of Antioxidant Peptides from Corn Silk Tryptic Hydrolysate: An Integrated In Vitro-In Silico Approach.Antioxidants (Basel, Switzerland) · 2021Article
- Targeting NRF2 to treat cancer.Seminars in cancer biology · 2021Review
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15 authors.
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Abstract
The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors, the activity of Nrf2 is inhibited by its interaction with the Keap1 (kelch-like ECH-associated protein 1). Here, we describe (3S)-1-[4-[(2,3,5,6-tetramethylphenyl) sulfonylamino]-1-naphthyl]pyrrolidine-3-carboxylic acid (RA839), a small molecule that binds noncovalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of ∼6 μM, as demonstrated by x-ray co-crystallization and isothermal titration calorimetry. Whole genome DNA arrays showed that at 10 μM RA839 significantly regulated 105 probe sets in bone marrow-derived macrophages. Canonical pathway mapping of these probe sets revealed an activation of pathways linked with Nrf2 signaling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knock-out macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me), RA839 prevented the induction of both inducible nitric-oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice, RA839 acutely induced Nrf2 target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2.
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