Kelch-like ECH-associated protein 1 (KEAP1)
KEAP1 (Kelch-like ECH-associated protein 1) is a cytoplasmic regulatory protein best known for controlling the stability of nuclear factor erythroid 2-related factor 2 (Nrf2), a central transcription factor in cellular antioxidant defense.
KEAP1 (Kelch-like ECH-associated protein 1) is a cytoplasmic regulatory protein best known for controlling the stability of nuclear factor erythroid 2-related factor 2 (Nrf2), a central transcription factor in cellular antioxidant defense. Under basal conditions, KEAP1 functions as part of a Cullin3-based ubiquitin ligase complex that promotes Nrf2 degradation, thereby limiting activation of antioxidant and cytoprotective genes. When KEAP1-mediated repression is reduced, Nrf2 can accumulate, translocate to the nucleus, and induce downstream protective programs such as heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Biomedically, KEAP1 is important because it sits at the center of the KEAP1-Nrf2 axis, a pathway implicated in oxidative stress responses, ischemic injury, diabetic nephropathy, septic acute kidney injury, Parkinson’s disease-related biology, and broader context-dependent stress adaptation. Recent work also highlights that KEAP1 pathway behavior is not determined solely by mutation status; rather, pathway output can vary with cellular context, protein interactions, and post-translational regulation.
Where the papers sit
24 papers from the last 6 months study Kelch-like ECH-associated protein 1 (KEAP1) directly · updated from PubMed 10 Oct 2026
Study type 0 clinical trials · 2 human data · 21 preclinical · 1 unclassified
Themes one subject · 1 paradigm shift
Those 24 are all about one subject.
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Oxidative Stress Signaling
KEAP1-NRF2 signaling is being studied as a common regulator of oxidative injury across cancer, metabolic disease, inflammation, neurotoxicity, and tissue repair. Most reports seek to activate NRF2 or disrupt the KEAP1-NRF2 interaction, while selected cancer studies instead exploit oxidative stress and ferroptosis. Candidate interventions include omaveloxolone, GSK3227634, 4-95, sesamin, natural products, and nanoparticles. Evidence remains largely preclinical, with disease-specific mechanisms and clinical benefit still unresolved.
KEAP1 disruption and NRF2 hyperactivation can create, rather than prevent, cancer-treatment vulnerability
The pancreatic ductal adenocarcinoma CAR T-cell study and the DMAMCL-treated neuroblastoma study both challenge the assumption that KEAP1 loss or NRF2 activation is uniformly cytoprotective. In pancreatic tumors, genetic KEAP1 ablation or clinically observed KEAP1/NFE2L2 mutations enhanced susceptibility to CAR T-cell killing, while in MYCN-amplified neuroblastoma, DMAMCL binding to KEAP1 increased nuclear NRF2 and HMOX1, thereby inducing ferroptosis. Together, these findings make KEAP1-NRF2 hyperactivation a context-dependent therapeutic liability that can be exploited to improve tumor killing, rather than treating it only as a stress-resistance mechanism 42826199Oct 42444025Jul.
Papers
The 24 papers from the last 6 months that study Kelch-like ECH-associated protein 1 (KEAP1) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Oxidative Stress Signaling (24)
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer. Science advances · 2 Oct 2026 PMID 42826199
- Effect of Lactiplantibacillus plantarum SCS6 on pancreatic oxidative damage in mice with type 2 diabetes based on gut-pancreas axis. Antonie van Leeuwenhoek · 15 Sept 2026 PMID 42742757
- A Subcellular Keap1-Nrf2 Disruption Strategy for Atopic Dermatitis Therapy. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720490
- The Discovery of GSK3227634: A Potent Inhaled Inhibitor of the KEAP1/NRF2 Protein-Protein Interaction for the Treatment of Chronic Obstructive Pulmonary Disease. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720473
- Dysregulated m6A via compensatory arginine methylation primes premalignancy in metabolic dysfunction-associated steatotic liver disease. Science advances · 9 Sept 2026 PMID 42715338
- Neuroprotective Effects of Cistanoside A against Cadmium-induced Neurotoxicity via Keap1/Nrf2/NF-kB Signaling: In Vivo and In Silico approaches. Molecular neurobiology · 1 Sept 2026 PMID 42678483
- Sesamin Promotes Diabetic Wound Healing by Inhibiting Ferroptosis via the SIRT1/Keap1/Nrf2 Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 31 Aug 2026 PMID 42671318
- Caulerpa peltata extract protects against Dextran sodium sulfate-induced acute ulcerative colitis via modulating Nrf2 pathway. Die Naturwissenschaften · 26 Aug 2026 PMID 42645156
- Integrated In Silico Discovery of Thymoquinone Analogs Targeting the Keap1-Nrf2 Pathway for Amyotrophic Lateral Sclerosis Therapy. ChemistryOpen · 19 Aug 2026 PMID 42613775
- Cross-Kingdom miR5054 Delivery via Polygonum cuspidatum-Derived Nanoparticles Enhances Burn Wound Healing by Regulating Microvascular Environment. ACS nano · 18 Aug 2026 PMID 42611244
- DMAMCL induces ferroptosis in neuroblastoma by targeting HMOX1 in MYCN-amplified subtypes whereas targeting STEAP3 in MYCN-nonamplified subtypes. Redox report : communications in free radical research · 14 Jul 2026 PMID 42444025
- XPO1 inhibition induces NCOR1-Dependent oxidative stress to suppress hepatocellular carcinoma. Cell chemical biology · 7 Jul 2026 PMID 42413506
- Clinical Outcomes Associated with Single STK11 Mutations and Those Co-occurring with KEAP1 and KRAS Mutations in Metastatic Non-Small Cell Lung Cancer. Advances in therapy · 30 Jun 2026 PMID 42377736
- Radio-Protective Effects of Selenium Nanoparticles Synthesized Using Aqueous Extract of Rhodiola on Mice Irradiated by 60Co γ-Rays. ACS biomaterials science & engineering · 23 Jun 2026 PMID 42335449
- A Keap1-Nrf2 protein-protein interaction inhibitor 4-95 ameliorates cognitive dysfunction by suppressing neuronal ferroptosis. Bioorganic chemistry · 20 Jun 2026 PMID 42322910
- Pharmacological Activation of NRF2 by Omaveloxolone Upregulates NRF2-Target Proteins in SMA Type I Human Fibroblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 16 Jun 2026 PMID 42301137
- Exosomal MALAT1 expression associated with the cardioprotective effects of carvacrol in acute doxorubicin-induced cardiac injury: Potential involvement of Nrf2/Keap1-related signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 8 Jun 2026 PMID 42259137
- Chemical Profiling and Scaffold-Based Drug-Discovery Analysis of Bioactive Compounds from Ceratonia siliqua L. with Computational and Biological Validation. Journal of chemical information and modeling · 28 May 2026 PMID 42206975
- Antidiabetic and antioxidant potentials of the ethyl acetate fraction of Momordica charantia leaf methanolic extract: in vitro and in silico studies. Bioorganic chemistry · 20 May 2026 PMID 42160833
- Poliumoside alleviates oxidative stress and improves mitochondrial function to alleviate ischemic stroke injury. European journal of pharmacology · 14 May 2026 PMID 42134761
- Cafestol ameliorates diabetic nephropathy via Keap1-Nrf2 axis activation: A novel renoprotective mechanism independent of glycemic control. PloS one · 14 May 2026 PMID 42133719
- TRIM16 attenuates TDP43-mediated oxidative injury by coordinating Nrf2 activation and TFR1 autophagic degradation. Free radical biology & medicine · 7 May 2026 PMID 42092406
- The protective effects and material basis of Astragalus membranaceus in the prevention and treatment of radiation-induced lung injury via modulation of the Keap1-Nrf2 signaling pathway. Journal of ethnopharmacology · 26 Apr 2026 PMID 42035997
- Phosphorylation of Cullin3 by the pseudokinase ALDH18A1 disrupts KEAP1-mediated NRF2 degradation. Biochemical and biophysical research communications · 17 Apr 2026 PMID 41996736
By study type
Human data, design not indexed (2)
- Integrated In Silico Discovery of Thymoquinone Analogs Targeting the Keap1-Nrf2 Pathway for Amyotrophic Lateral Sclerosis Therapy. ChemistryOpen · 19 Aug 2026 PMID 42613775
- Chemical Profiling and Scaffold-Based Drug-Discovery Analysis of Bioactive Compounds from Ceratonia siliqua L. with Computational and Biological Validation. Journal of chemical information and modeling · 28 May 2026 PMID 42206975
Preclinical: animal, cell and lab studies (21)
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer. Science advances · 2 Oct 2026 PMID 42826199
- Effect of Lactiplantibacillus plantarum SCS6 on pancreatic oxidative damage in mice with type 2 diabetes based on gut-pancreas axis. Antonie van Leeuwenhoek · 15 Sept 2026 PMID 42742757
- A Subcellular Keap1-Nrf2 Disruption Strategy for Atopic Dermatitis Therapy. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720490
- The Discovery of GSK3227634: A Potent Inhaled Inhibitor of the KEAP1/NRF2 Protein-Protein Interaction for the Treatment of Chronic Obstructive Pulmonary Disease. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720473
- Dysregulated m6A via compensatory arginine methylation primes premalignancy in metabolic dysfunction-associated steatotic liver disease. Science advances · 9 Sept 2026 PMID 42715338
- Neuroprotective Effects of Cistanoside A against Cadmium-induced Neurotoxicity via Keap1/Nrf2/NF-kB Signaling: In Vivo and In Silico approaches. Molecular neurobiology · 1 Sept 2026 PMID 42678483
- Sesamin Promotes Diabetic Wound Healing by Inhibiting Ferroptosis via the SIRT1/Keap1/Nrf2 Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 31 Aug 2026 PMID 42671318
- Caulerpa peltata extract protects against Dextran sodium sulfate-induced acute ulcerative colitis via modulating Nrf2 pathway. Die Naturwissenschaften · 26 Aug 2026 PMID 42645156
- Cross-Kingdom miR5054 Delivery via Polygonum cuspidatum-Derived Nanoparticles Enhances Burn Wound Healing by Regulating Microvascular Environment. ACS nano · 18 Aug 2026 PMID 42611244
- DMAMCL induces ferroptosis in neuroblastoma by targeting HMOX1 in MYCN-amplified subtypes whereas targeting STEAP3 in MYCN-nonamplified subtypes. Redox report : communications in free radical research · 14 Jul 2026 PMID 42444025
- XPO1 inhibition induces NCOR1-Dependent oxidative stress to suppress hepatocellular carcinoma. Cell chemical biology · 7 Jul 2026 PMID 42413506
- Radio-Protective Effects of Selenium Nanoparticles Synthesized Using Aqueous Extract of Rhodiola on Mice Irradiated by 60Co γ-Rays. ACS biomaterials science & engineering · 23 Jun 2026 PMID 42335449
- A Keap1-Nrf2 protein-protein interaction inhibitor 4-95 ameliorates cognitive dysfunction by suppressing neuronal ferroptosis. Bioorganic chemistry · 20 Jun 2026 PMID 42322910
- Pharmacological Activation of NRF2 by Omaveloxolone Upregulates NRF2-Target Proteins in SMA Type I Human Fibroblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 16 Jun 2026 PMID 42301137
- Exosomal MALAT1 expression associated with the cardioprotective effects of carvacrol in acute doxorubicin-induced cardiac injury: Potential involvement of Nrf2/Keap1-related signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 8 Jun 2026 PMID 42259137
- Antidiabetic and antioxidant potentials of the ethyl acetate fraction of Momordica charantia leaf methanolic extract: in vitro and in silico studies. Bioorganic chemistry · 20 May 2026 PMID 42160833
- Poliumoside alleviates oxidative stress and improves mitochondrial function to alleviate ischemic stroke injury. European journal of pharmacology · 14 May 2026 PMID 42134761
- Cafestol ameliorates diabetic nephropathy via Keap1-Nrf2 axis activation: A novel renoprotective mechanism independent of glycemic control. PloS one · 14 May 2026 PMID 42133719
- TRIM16 attenuates TDP43-mediated oxidative injury by coordinating Nrf2 activation and TFR1 autophagic degradation. Free radical biology & medicine · 7 May 2026 PMID 42092406
- The protective effects and material basis of Astragalus membranaceus in the prevention and treatment of radiation-induced lung injury via modulation of the Keap1-Nrf2 signaling pathway. Journal of ethnopharmacology · 26 Apr 2026 PMID 42035997
- Phosphorylation of Cullin3 by the pseudokinase ALDH18A1 disrupts KEAP1-mediated NRF2 degradation. Biochemical and biophysical research communications · 17 Apr 2026 PMID 41996736
Unclassified: not yet indexed with MeSH (1)
- Clinical Outcomes Associated with Single STK11 Mutations and Those Co-occurring with KEAP1 and KRAS Mutations in Metastatic Non-Small Cell Lung Cancer. Advances in therapy · 30 Jun 2026 PMID 42377736
Written from 24 PubMed abstracts, each one listed by PMID above. Published: 2026-07-02. Last written: 2026-09-03 by GPT. Drafted by language models from published abstracts; not medical advice.