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Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.
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http://dx.doi.org/10.1016/j.ejmech.2020.112532 | DOI Listing |
Front Biosci (Landmark Ed)
August 2025
Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-Sen University, 518107 Shenzhen, Guangdong, China.
Background: Adenocarcinoma of Lung (LUAD) remains a leading cause of cancer-related deaths across the globe, and patients harboring epidermal growth factor receptor (EGFR) mutations frequently develop resistance to targeted therapies. While aurora kinase A (AURKA) has been implicated in tumorigenesis, its involvement in regulating ferroptosis via the kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2)/heme oxygenase 1 (HO‑1) signaling axis in EGFR-mutant LUAD remains poorly understood.
Methods: We analyzed RNA-seq and clinical data from 594 LUAD samples from The Cancer Genome Atlas (TCGA) to explore associations between AURKA expression, EGFR mutation status, and immune cell infiltration.
ChemMedChem
September 2025
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) axis is an attractive therapeutic target for various intractable diseases. Although protein-protein interaction inhibitors against Keap1-Nrf2 have been developed over the past decade, more structural expansion is needed to improve efficacy. In this article, several candidate compounds are designed and synthesized as novel Nrf2 activators and their intracellular Nrf2-activating effects are evaluated.
View Article and Find Full Text PDFBr J Cancer
September 2025
Department of Biochemistry and Molecular Biology, Tohoku University, Tohoku Medical Megabank Organization, Sendai, Japan.
Background: The development and clinical success of KRAS inhibitors was a landmark achievement in anti-cancer drug development, as oncogenic KRAS had long been considered an intractable therapeutic target. Patients with KRAS mutant lung cancers frequently present with co-mutations in the KEAP1-NRF2 pathway, and because genetic activation of NRF2 results in resistance to all current anti-cancer therapies, we were motivated to explore how aberrant activation of NRF2 impacts the clinical response to KRAS inhibitors.
Methods: A broad range of techniques, including genetic knockouts, scRNA-seq and surface plasmon resonance, were used to determine the effect of KRAS drugs on NRF2.
J Mol Histol
August 2025
Department of Internal Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.
Background: Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.
View Article and Find Full Text PDFInt Immunopharmacol
August 2025
Clinical Trial Institution, Affiliated Hospital of Jiangnan University, Wuxi, China. Electronic address:
Alcoholic liver disease (ALD) poses a significant global health burden and has limited therapeutic options. This study investigates the therapeutic efficacy of piceatannol (PIC) in mice with pre-existing ALD. In vivo, during the last 2 weeks of the 6-week ethanol model establishment process, PIC treatment was able to alleviate liver inflammation, oxidative stress and ferroptosis.
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