ArticleOncotarget2017
Discovery of a novel Nrf2 inhibitor that induces apoptosis of human acute myeloid leukemia cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 45 citations in OpenAlex.
- Lipid peroxidation in cancer: a double-edged sword shaping progression and therapy.Medical oncology (Northwood, London, England) · 2026Review
- Capicua mediates interleukin-2 withdrawal-induced death of activated CD8Cell insight · 2026Article
- Potential of Apigenin, Berberine, Chrysin, and Luteolin to Overcome Doxorubicin Resistance in Acute Promyelocytic Leukemia HL-60 Cells.International journal of molecular sciences · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- Review
- Glutathione dynamics in subcellular compartments and implications for drug development.Current opinion in chemical biology · 2024Review
- Milk Fat Globule Membrane Relieves Fatigue via Regulation of Oxidative Stress and Gut Microbiota in BALB/c Mice.Antioxidants (Basel, Switzerland) · 2023Article
- NRF2 and the Moirai: Life and Death Decisions on Cell Fates.Antioxidants & redox signaling · 2023Review
- Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung cancer A549 cells.Toxicology research · 2022Article
- Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2.Cell death & disease · 2022Article
- The Nrf2 inhibitor brusatol synergistically enhances the cytotoxic effect of lapatinib in HER2-positive cancers.Heliyon · 2022Article
- The molecular biology and therapeutic potential of Nrf2 in leukemia.Cancer cell international · 2022Review
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Schisantherin A improves learning and memory abilities partly through regulating the Nrf2/Keap1/ARE signaling pathway in chronic fatigue mice.Experimental and therapeutic medicine · 2021Article
- Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas.Frontiers in pharmacology · 2021Article
- Hypoxia-inducible factor 1 (HIF-1) is a new therapeutic target in JAK2V617F-positive myeloproliferative neoplasms.Leukemia · 2020Article
- Potential Applications of NRF2 Modulators in Cancer Therapy.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor-erythroid 2-related factor 2 (Nrf2) is persistently activated in many human tumors including acute myeloid leukemia (AML). Therefore, inhibition of Nrf2 activity may be a promising target in leukemia therapy. Here, we used an antioxidant response element-luciferase reporter system to identify a novel pyrazolyl hydroxamic acid derivative, 1-(4-(tert-Butyl)benzyl)-3-(4-chlorophenyl)-N-hydroxy-1H pyrazole-5-carboxamide (4f), that inhibited Nrf2 activity. 4f had a profound growth-inhibitory effect on three AML cell lines, THP-1, HL-60 and U937, and a similar anti-growth effect in a chick embryo model. Moreover, flow cytometry of AML cells revealed increased apoptosis with 4f (10 μM) treatment for 48 h. The protein levels of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase were enhanced in all three AML cell types. Furthermore, Nrf2 protein level was downregulated by 4f. Upregulation of Nrf2 by tert-butylhydroquinone (tBHQ) or Nrf2 overexpression could ameliorate 4f-induced growth inhibition and apoptosis. Treatment with 4f reduced both B-cell lymphoma-2 (Bcl-2) expression and Bcl-2/Bcl-2-associated X protein (Bax) ratio, which indicated that 4f induced apoptosis, at least in part, via mitochondrial-dependent signaling. Therefore, as an Nrf2 inhibitor, the pyrazolyl hydroxamic acid derivative 4f may be a promising agent in AML therapy.
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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.