ArticleACS pharmacology & translational science2023
Cell-Permeable PROTAC Degraders against KEAP1 Efficiently Suppress Hepatic Stellate Cell Activation through the Antioxidant and Anti-Inflammatory Pathway.
Article in ACS pharmacology & translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 30 citations in OpenAlex.
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.Acta pharmaceutica Sinica. B · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions.Bioconjugate chemistry · 2024Review
- Recent insights of PROTAC developments in inflammation-mediated and autoimmune targets: a critical review.RSC medicinal chemistry · 2024Review
- Emerging Landscape of Supercharged Proteins and Peptides for Drug Delivery.ACS pharmacology & translational science · 2024Review
- Specific targeting of the NRF2/β-TrCP axis promotes beneficial effects in NASH.Redox biology · 2024Article
- Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches.ACS pharmacology & translational science · 2024Review
- Incorporating a β-hairpin sequence motif to increase intracellular stability of a peptide-based PROTAC.Biochemical engineering journal · 2023Article
- Research in the Field of Drug Design and Development.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Development of KEAP1-targeting PROTAC and its antioxidant properties: In vitro and in vivo.Redox biology · 2023Article
- Delivery of Oleanolic Acid with Improved Antifibrosis Efficacy by a Cell Penetrating Peptide P10.ACS pharmacology & translational science · 2023Article
- Emerging Landscape of Cell-Penetrating Peptide-Mediated Organelle Restoration and Replacement.ACS pharmacology & translational science · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates that oxidative stress and inflammation are involved in the physiopathology of liver fibrogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor, which regulates the expression of redox regulators to establish cellular redox homeostasis. The Nrf2 modulator can serve as a primary cellular defense against the cytotoxic effects of oxidative stress. We designed a chimeric Keap1-Keap1 peptide (KKP1) based on the proteolysis-targeting chimera technology. The KKP1 peptide not only can efficiently penetrate into the rat hepatic stellate cell line (HSC-T6) cells but also can induce Keap1 protein degradation by the ubiquitination-proteasome degradation pathway, which releases Nrf2 and promotes the transcriptional activity of the Nrf2/antioxidant response element pathway. It then activates the protein expression of the downstream antioxidant factors, the glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 (HO-1). Finally, Keap1 protein degradation inhibits the nuclear factor-kappaB inflammatory signal pathway, the downstream inflammatory factor tumor necrosis factor alpha, and the interleukin-1beta protein expression and further inhibits the expression of the fibrosis biomarker gene. The current research suggests that our designed KKP1 may provide a new avenue for the future treatment of liver fibrosis.
Identifiers
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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.