ArticleAdvanced materials (Deerfield Beach, Fla.)2024
Inhibiting the Keap1/Nrf2 Protein-Protein Interaction with Protein-Like Polymers.
Article in Advanced materials (Deerfield Beach, Fla.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Mdivi-1 augments chlorpromazine's anticancer effect via modulation of mitochondrial dynamics, hallmarks of cancer-related cellular behavior, and oxidative stress.Medical oncology (Northwood, London, England) · 2026Article
- Angiotensin (1-7)-based Proteomimetic Polymers as Topicals for the Remediation and Repair of the Cornea following Injury.bioRxiv : the preprint server for biology · 2026Article
- Review
- How phosphorylation of α/β-tubulin perturbs microtubule structure: A computational study.The Journal of biological chemistry · 2026Article
- Amphipathic β‑Sheet-Forming Octapeptide Self-Assembly Using the Martini Potential Family.ACS omega · 2026Article
- Advancing Treatment of Degenerative Eye Diseases at the Nanoscale.Smart medicine · 2026Review
- Strategic physicochemical tuning: amphiphilic polymers as molecular regulators of amyloid aggregation and cytotoxicity.Chemical science · 2026Article
- Review
- Tuning Polyacrylate Composition to Recognize and Modulate Fluorescent Proteins.Angewandte Chemie (International ed. in English) · 2026Article
- Artesunate Targets MBL2 to Modulate the TLR4/NRF2/HO‑1 Axis and Ameliorate Podophyllotoxin‑Induced Liver Injury.Drug design, development and therapy · 2026Article
- Identification of a novel and high-affinity cyclic peptide targeting Keap1 for inflammation treatment by a combined virtual screening strategy.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Seeking Precise Protein-like Functions from Random Heteropolymer Ensemble and through Dimensionality Reduction.ACS central science · 2025Review
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- PLZF promotes compensatory lung growth by increasing HPMEC proliferation and angiogenesis.PloS one · 2025Article
- Polymers for Disrupting Protein-Protein Interactions: Where Are We and Where Should We Be?Biomacromolecules · 2024Review
- Ferroptosis-related oxaliplatin resistance in multiple cancers: Potential roles and therapeutic Implications.Heliyon · 2024Review
- Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.Biomolecules · 2024Article
- The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease.Theranostics · 2024Article
- The Nrf2-HO-1 system and inflammaging.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Successful and selective inhibition of the cytosolic protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein 1 (Keap1) can enhance the antioxidant response, with the potential for a therapeutic effect in a range of settings including in neurodegenerative disease (ND). Small molecule inhibitors have been developed, yet many have off-target effects, or are otherwise limited by poor cellular permeability. Peptide-based strategies have also been attempted to enhance specificity, yet face challenges due to susceptibility to degradation and lack of cellular penetration. Herein, these barriers are overcome utilizing a polymer-based proteomimetics. The protein-like polymer (PLP) consists of a synthetic, lipophilic polymer backbone displaying water soluble Keap1-binding peptides on each monomer unit forming a brush polymer architecture. The PLPs are capable of engaging Keap1 and displacing the cellular protective transcription factor Nrf2, which then translocates to the nucleus, activating the antioxidant response element (ARE). PLPs exhibit increased Keap1 binding affinity by several orders of magnitude compared to free peptides, maintain serum stability, are cell-penetrant, and selectively activate the ARE pathway in cells, including in primary cortical neuronal cultures. Keap1/Nrf2-inhibitory PLPs have the potential to impact the treatment of disease states associated with dysregulation of oxidative stress, such as NDs.
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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.