ArticleMolecular and cellular biology2020
Geldanamycin-Derived HSP90 Inhibitors Are Synthetic Lethal with NRF2.
Article in Molecular and cellular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 52 citations in OpenAlex.
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- Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.Biochemical genetics · 2026Review
- Identification of drug candidates against glioblastoma with machine learning and high-throughput screening of heterogeneous cellular models.Digital discovery · 2026Article
- Long noncoding RNAs at the crossroads of smoking, oxidative stress, inflammation, and lung disease.Archives of toxicology · 2026Review
- Gambogic acid ameliorates hepatocellular carcinoma by inhibiting oxidative stress via Nrf2-pSmad2C/2L pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Asiaticoside protects against PDF-induced peritoneal fibrosis via suppression of AhR/Nrf2-mediated MMT and oxidative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Crosstalk Between the NRF2 Signaling Pathway and Heat Shock Proteins: Implications for Cellular Stress Response and Disease Therapy.Oxidative medicine and cellular longevity · 2026Review
- Theobromine as a molecular switch: targeting Nrf2 pathway in invasive and non-invasive bladder cancer.Journal of natural medicines · 2026Article
- Nanoencapsulated Syzygium aromaticum oil alleviates acetic acid-induced ulcerative colitis in rats by influencing critical redox, NF-κB/iNOS, and Keap1/Nrf2/HO-1 signaling pathways.Inflammopharmacology · 2025Article
- Systemic activation of NRF2 contributes to the therapeutic efficacy of clinically-approved KRAS-G12C anti-cancer drugs.British journal of cancer · 2025Article
- A novel anti-acute lung injury mechanism of astilbin: inhibition of epithelial cells ferroptosis by targeting NRF2 activation via binding Val608 site of NRF2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Sheep Pox Susceptibility: Role of Genetic Variants, Gene Expression, and Immune-Oxidative Markers.Veterinary sciences · 2025Article
- NRF2 activation in cancer and overview of NRF2 small molecule inhibitors.Archives of pharmacal research · 2025Review
- Individual Genomic Loci, Transcript Levels, and Serum Profiles of Immune and Antioxidant Markers Associated with Bacteria-Induced Abortion in Sheep (Veterinary sciences · 2025Article
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- RepID depletion enhances TWS119-induced erythropoiesis through chromatin reprogramming and transcription factor recruitment.Genes & genomics · 2025Article
- Mechanism of action and new developments in the study of curcumin in the treatment of osteoarthritis: a narrative review.Inflammopharmacology · 2025Review
- Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.Journal of medicinal chemistry · 2024Review
- The Transcript Levels and the Serum Profile of Biomarkers Associated with Clinical Endometritis Susceptibility in Buffalo Cows.Veterinary sciences · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations in KEAP1-NRF2 are frequently found in tumors of the lung, esophagus, and liver, where they are associated with aggressive growth, resistance to cancer therapies, and low overall survival. Despite the fact that NRF2 is a validated driver of tumorigenesis and chemotherapeutic resistance, there are currently no approved drugs which can inhibit its activity. Therefore, there is an urgent clinical need to identify NRF2-selective cancer therapies. To this end, we developed a novel synthetic lethal assay, based on fluorescently labeled isogenic wild-type and Keap1 knockout cell lines, in order to screen for compounds which selectively kill cells in an NRF2-dependent manner. Through this approach, we identified three compounds based on the geldanamycin scaffold which display synthetic lethality with NRF2. Mechanistically, we show that products of NRF2 target genes metabolize the quinone-containing geldanamycin compounds into more potent HSP90 inhibitors, which enhances their cytotoxicity while simultaneously restricting the synthetic lethal effect to cells with aberrant NRF2 activity. As all three of the geldanamycin-derived compounds have been used in clinical trials, they represent ideal candidates for drug repositioning to target the currently untreatable NRF2 activity in cancer.
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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.