NRF2 activator 
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  • ||||||||||  Journal:  Alpha-ketoglutarate alleviates acute pancreatitis by restoring energy metabolism. (Pubmed Central) -  Apr 10, 2026   
    Mechanistically, AKG restored pancreatic energy metabolism and mitochondrial structure while reactivating the Nrf2 antioxidant and adenosine monophosphate-activated protein kinase signaling pathways. These findings highlight AKG as a specific metabolic signature of AP and a promising therapeutic agent for alleviating mitochondrial dysfunction and organ injury.
  • ||||||||||  Review, Journal:  P62 in colorectal cancer: from inflammation suppression to cancer promotion. (Pubmed Central) -  Apr 10, 2026   
    Excessive p62 also impairs DNA double-strand break repair, facilitating oncogenic mutations. These observations indicate that enhancing autophagic clearance of p62 could represent a promising therapeutic strategy to prevent inflammation-associated CRC.
  • ||||||||||  Journal:  Mechanistic study on PQQ improving the quality of aged bovine oocytes and early embryonic developmental potential via Nrf2-mediated redox signaling. (Pubmed Central) -  Apr 9, 2026   
    The results showed that supplementation with 10??mol/L PQQ significantly increased the cleavage rate and blastocyst rate of aged bovine oocytes; simultaneously, it significantly downregulated the mRNA expression level of Keap1 and upregulated the mRNA expression levels of Nrf2, Akt, and their downstream target genes (SOD1, SOD2, HO-1, NQO1, and GCLC).The protein expression levels determined by Western blotting were consistent with the mRNA expression levels detected. In conclusion, PQQ activates the Nrf2 pathway to reduce reactive oxygen species (ROS) accumulation, enhance mitochondrial function, inhibit apoptosis, thereby improving aged bovine oocytes' quality and developmental potential, providing a theoretical and practical reference for optimizing bovine oocyte IVM systems.
  • ||||||||||  Journal:  Ultrasound and ROS-responsive nanodroplets inhibit TCA cycle in hepatocellular carcinoma. (Pubmed Central) -  Apr 8, 2026   
    This dual action synergistically inhibits the TCA cycle, resulting in an antitumor efficacy of up to 95.1%, which is significantly higher than that observed in the control groups. Thus, the combination of sGTND and UTMD can effectively inhibit the TCA cycle through NRF2 activation and G6PD inhibition, which represents a promising therapeutic approach for HCC.
  • ||||||||||  Journal:  Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells. (Pubmed Central) -  Apr 8, 2026   
    Finally, we show that NRF2 activation creates a sensitivity to high environmental cystine, which impairs cell proliferation through excess free cysteine, and can be mitigated by sequestration into cysteine-derived conjugates. Overall, these findings reveal a cancer-associated metabolic vulnerability to excess cysteine stress, and reveal unrecognized routes of cysteine metabolism.
  • ||||||||||  Journal:  H2-driven autonomous pore-forming hydrogel promotes rapid vascularization for dry socket healing. (Pubmed Central) -  Apr 8, 2026   
    Notably, DS implantation models revealed that Mg/Gel mitigates excessive inflammation responses in the early DS healing stage and enhances angiogenesis in the proliferative stage, thereby facilitating alveolar bone regeneration. These data suggest that our H2-releasing Mg/Gel with self-assembling porous structure spatiotemporally coordinates the healing, thus offering a transformative strategy for DS treatment.
  • ||||||||||  Journal, IO biomarker:  The NRF2 readout beyond genotyping (Pubmed Central) -  Apr 8, 2026   
    These data suggest that our H2-releasing Mg/Gel with self-assembling porous structure spatiotemporally coordinates the healing, thus offering a transformative strategy for DS treatment. We discuss the next steps towards clinical translation, including prospective NRF2 activation-state stratification, integration of immune context for immunotherapy, and biomarker evaluation of redox and metabolic combinations based on NRF2-associated vulnerabilities.
  • ||||||||||  dexmedetomidine / Generic mfg.
    Preclinical, Journal:  A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and ?2-adrenergic receptor signaling pathway. (Pubmed Central) -  Apr 3, 2026   
    Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and ?2-adrenergic receptor (?2-AR) activation by dexmedetomidine (Dex)...Notably, ?2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1 + cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.
  • ||||||||||  Journal:  GSTA1 Depletes Glutathione and Exacerbates Oxidative Stress in ?-Amanitin-Induced Hepatotoxicity. (Pubmed Central) -  Apr 1, 2026   
    This study unveils a novel mechanism where ?-AMA hijacks the NRF2-GSTA1 antioxidant axis, transforming GSTA1 from a detoxifier into a key perpetrator of hepatotoxicity via GSH depletion, ROS overproduction. GSTA1 emerges as a promising direct therapeutic target and potential diagnostic biomarker for ?-AMA poisoning, highlighting a critical direction for future research.
  • ||||||||||  bortezomib / Generic mfg.
    Journal:  Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK?Nrf2 axis in multiple myeloma. (Pubmed Central) -  Apr 1, 2026   
    In contrast, the methylation status of histone H3 lysine 4 (H3K4me1/3) on the PERK promoter remains unaltered, regardless of the complex state. Taken together, the findings of this study underscore the key role of KDM5C as a driving force behind MM progression and BTZ resistance, indicating that KDM5C represents a novel and promising therapeutic target for the treatment of BTZ-resistant MM.
  • ||||||||||  Journal:  ?-Lipoic Acid Activates the Nrf2/HO-1 Pathway to Ameliorate Arsenic-Induced Multiorgan Oxidative Damage. (Pubmed Central) -  Apr 1, 2026   
    Importantly, siRNA-mediated knockdown of Nrf2 significantly inhibited the protective effects of ?-LA. These findings reveal that ?-LA counteracts arsenic-induced multiorgan oxidative damage by activating the Nrf2/HO-1 signaling axis, highlighting its potential as an intervention for populations exposed to agricultural arsenic and warranting further clinical investigation.
  • ||||||||||  Review, Journal:  Activation of Nrf2 with natural flavonoids and mesenchymal stromal/stem cells: mechanisms and therapeutic potential for inflammatory diseases. (Pubmed Central) -  Apr 1, 2026   
    This review focuses on the activation mechanisms of Nrf2 and its clinical and preclinical inducers, with particular emphasis on the mechanistic insights and therapeutic applications of natural flavonoids and MSCs in the prevention or treatment of inflammatory diseases. More importantly, it summarizes the profound role of flavonoid-MSCs combinatorial therapy in the intervention of inflammatory diseases, pointing out novel therapeutic strategies and future prospects for modulating the Nrf2 signaling pathway in the treatment of inflammatory disorders.
  • ||||||||||  Preclinical, Review, Journal:  Mouse Models of Diabetic Complications: Dissecting Molecular Mechanisms of Disease Progression. (Pubmed Central) -  Apr 1, 2026   
    Therapeutic strategies targeting these conserved molecular pathways-including Nrf2 activation, NF-?B inhibition, or mitochondrial restoration-have demonstrated efficacy across multiple models. By aligning pathophysiological mechanisms with appropriate experimental systems, this review provides a practical framework for selecting preclinical tools and developing multi-targeted interventions to prevent or slow the progression of diabetic complications.
  • ||||||||||  Journal:  Hirsutine mitigates high glucose-induced cell injury via autophagy activation and NRF2/GPX4-mediated ferroptosis inhibition. (Pubmed Central) -  Apr 1, 2026   
    Hirsutine increased the markers of NRF2 pathway activation and also reduced the biochemical signatures consistent with ferroptosis.This study provides new evidence that hirsutine protects against HG-induced cell injury by simultaneously modulating apoptosis, autophagy and ferroptosis, highlighting its potential as a candidate for future DN therapy. However, these results are limited to an in vitro model and lack direct autophagic flux assessment and genetic validation of NRF2 dependency, which warrant further investigation.
  • ||||||||||  Journal:  ADAMTS13 ameliorates diabetic nephropathy by Nrf2/GPX4/eNOS signaling pathway. (Pubmed Central) -  Apr 1, 2026   
    Our findings suggest that ADAMTS13 may be a potential therapeutic agent for DN through Nrf2/GPX4/eNOS signaling pathway. ADAMTS13 may alleviate DN by inhibiting modulating ferroptosis through the regulation of mitophagy, thereby ameliorating endothelial dysfunction.
  • ||||||||||  Biomarker, Review, Journal, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker:  Molecular subtyping-guided precision therapy for ESCC: biomarker-driven strategies and clinical translation pathways. (Pubmed Central) -  Apr 1, 2026   
    Translating subtyping into clinical practice requires validating strategies through innovative trial designs, establishing dynamic monitoring using liquid biopsy and spatial multiomics, and integrating multidimensional biomarkers. Constructing a molecular subtype-based precision medicine framework is pivotal to overcoming therapeutic limitations and improving survival in ESCC.
  • ||||||||||  Preclinical, Journal, IO biomarker:  Daixie recipe ameliorates diet-induced MASH in mice via activating PI3K/AKT and Keap1/Nrf2 signaling. (Pubmed Central) -  Apr 1, 2026   
    Its mechanism of action involves the suppression of lipid synthesis and the prevention of hepatocyte apoptosis, achieved by modulating key anti-inflammatory and antioxidant signaling pathways. Flavonoids (such as apigenin and quercetin) are identified as the key active ingredients in DXR responsible for activating Keap1/Nrf2 and PI3K/AKT signaling pathways.
  • ||||||||||  Journal:  A mechanistic study of mitochondria-targeted PCSK9 liposomes attenuate oxidative damage in carotid artery plaques. (Pubmed Central) -  Apr 1, 2026   
    Further analysis by Western blot and transcriptomics revealed that TPP-LIP@PCSK9 downregulated the mitochondrial damage marker proteins PINK1/Parkin, activated the Nrf2/UCP2-mediated antioxidant pathway, and modulated signaling pathways closely associated with oxidative stress and metabolism. This study is the first to report the direct role of PCSK9 in mitochondrial oxidative damage within plaque endothelial cells and to achieve effective intervention via nanotechnology, providing a new perspective for the treatment of atherosclerosis.
  • ||||||||||  Skyclarys (omaveloxolone) / Biogen, Vtama (tapinarof) / Organon
    Review, Journal:  NRF2 as a Therapeutic Target in Dermatological Disorders: Mechanisms and Molecules. (Pubmed Central) -  Mar 28, 2026   
    Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress-driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice.
  • ||||||||||  calcifediol / Generic mfg.
    Review, Journal:  Vitamin D3 as an immunomodulatory agent: molecular mechanisms, clinical translation, and precision therapeutic strategies. (Pubmed Central) -  Mar 18, 2026   
    Novel delivery systems-nanoemulsions, twin-screw extrusion technology, and liposomes-effectively overcome bioavailability and stability limitations of traditional preparations. This review systematically examines the immunomodulatory mechanisms of Vitamin D3, evaluates clinical translation evidence in psoriasis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and discusses precision medicine strategies and therapeutic potential.
  • ||||||||||  IPN60090 / UT MD Anderson Cancer Center, Ipsen
    Inhibiting glutamine metabolism in combination with radiation disrupts mitochondrial function and impairs homologous recombination (Section 17) -  Mar 17, 2026 - Abstract #AACR2026AACR_9843;    
    Our results identified that the inhibitor IACS-6274, which inhibits GLS1, increased total DNA damage measured by the alkaline comet assay but abrogated foci formation for both phosphorylated-ATM and Rad51 (homologous recombination [HR])...In parallel, we determined that mitochondrial membrane potential measured using the dye, TMRM, is significantly reduced along with reduced ATP production in GLS1 inhibited cells.In summary, our results show that KEAP1 mutant lung cancer cells treated with a GLS1 inhibitor can be significantly radiosensitized to radiotherapy, and this in part maybe attributable to reduced HR proficiency. We propose that either bioenergetic crisis prevents fueling of HR processes or that impaired TCA cycle anaplerosis reduces ?-ketogluterate levels, which is an important co-factor for chromatin remodeling preventing DNA end resection and resulting Rad51 foci formation.
  • ||||||||||  Nrf2 as a therapeutic target to improve T cell function in muscle invasive bladder cancer (MIBC) (Section 45) -  Mar 17, 2026 - Abstract #AACR2026AACR_8774;    
    Together, these findings identify a previously unrecognized T cell intrinsic role of Nrf2 in suppressing antitumor immunity and promoting bladder cancer progression. Our work highlights Nrf2 as an immune checkpoint for T cells and indicates its targeting as a promising therapeutic strategy, especially in synergy with current immunotherapies, to improve MIBC patient outcomes.