ArticleJournal of medicinal chemistry2024
Covalent Inhibitors of KEAP1 with Exquisite Selectivity.
Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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
6 citing papers in PubMed.
- Epidermal Growth Factor Receptor as a Model Drug Target for Scrutinizing the Status Quo in Drug Discovery and Chemical Biology.ACS bio & med chem Au · 2026Review
- An ML-Based QSAR Web Server for KEAP1 Inhibitor Bioactivity Prediction: Composite-Score-Driven Training and Advanced Validation.ACS omega · 2026Article
- Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.Biochemical genetics · 2026Review
- Design, Synthesis, and Biological Evaluation of Novel Vinyl Selenone Derivatives as Potent Nrf2 Activators for Atopic Dermatitis.Journal of medicinal chemistry · 2026Article
- The KEAP1-Cullin3-RBX1-Nrf2 Axis in Redox Homeostasis: Molecular Mechanisms, Pathophysiological Roles, and Precision Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.Journal of medicinal chemistry · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NRF2-KEAP1 interaction is central for cytoprotection against stresses, giving it high clinical significance. Covalent modification of KEAP1 is an efficient approach, but the covalent inhibitors used in the clinic carry undesired side effects originating in their moderate selectivity. Starting with a phenotypic screen, we identified a new covalent inhibitor chemotype that was optimized to deliver a series of potent and highly selective KEAP1 binders. While the developed compounds showed both cellular and in vivo activity, upregulating antioxidant response element-dependent target genes, they showed no genotoxicity in vitro. The lead compound exhibited broad selectivity in activity-based protein profiling and showed no significant interaction with a panel of commonly studied receptors nor with a broad panel of kinases. The nature of its interaction with KEAP1 and the origin of its selectivity were revealed by X-ray crystallography.
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Registered trials
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