ArticleCell chemical biology2018
ALDH1 Bio-activates Nifuroxazide to Eradicate ALDH
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Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
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32 citing papers in PubMed, 59 citations in OpenAlex.
- Common human ALDH1B1 and ALDH2 variants increase neuroinflammatory response to a single ethanol dose in mice.Science advances · 2026Article
- Role of antidiarrheal agents nifuroxazide in antitumor multi‑target anticancer, multi‑mechanism anticancer drug (Review).Oncology letters · 2025Review
- Evaluating Vancomycin Monotherapy and Dual Therapy with Nifuroxazide for Medium-Severe Clostridioides Difficile Infection.Antibiotics (Basel, Switzerland) · 2025Article
- Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer.Nature communications · 2025Article
- The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024Review
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Nifuroxazide Prevents Chikungunya Virus Infection BothViruses · 2024Article
- Review
- ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.Cell reports · 2024Article
- Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.Molecules (Basel, Switzerland) · 2024Article
- Small Schiff Base Molecules-A Possible Strategy to Combat Biofilm-Related Infections.Antibiotics (Basel, Switzerland) · 2024Review
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Nifuroxazide Activates the Parthanatos to Overcome TMPRSS2:ERG Fusion-Positive Prostate Cancer.Molecular cancer therapeutics · 2023Article
- Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1.Nature chemical biology · 2022Article
- Development and Validation of a HPLC-MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice.Pharmaceutics · 2022Article
- Drug-Tolerant Persister Cells in Cancer Therapy Resistance.Cancer research · 2022Review
- New Potential Agents for Malignant Melanoma Treatment-Most Recent Studies 2020-2022.International journal of molecular sciences · 2022Review
- The Interplay between Tumour Microenvironment Components in Malignant Melanoma.Medicina (Kaunas, Lithuania) · 2022Review
- Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance.Frontiers in medicine · 2022Review
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Authors and funding
20 authors at 9 institutions in 2 countries.
Sana SarviMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Richard CrispinCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Yuting LuMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Lifan ZengDepartment of Biochemistry & Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive Medical Science, Indianapolis, IN 46202, USA.
Thomas D HurleyDepartment of Biochemistry & Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive Medical Science, Indianapolis, IN 46202, USA.
Douglas R HoustonSchool of Biological Sciences, University of Edinburgh, Waddington Building, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
Alex von KriegsheimCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Che-Hong ChenDepartment of Chemical and Systems Biology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305-5174, USA.
Daria Mochly-RosenDepartment of Chemical and Systems Biology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305-5174, USA.
Marco RanzaniExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK; Biology Team, Artios Pharma Limited, Meditrina (B 260), Babraham Research Campus, Cambridge CB22 3AT, UK.
Marie E MathersDepartment of Pathology, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Xiaowei XuDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wei XuAbramson Cancer Center University of Pennsylvania, Philadelphia, PA 19104, USA.
David J AdamsExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
Neil O CarragherCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Mayumi FujitaDepartment of Dermatology, University of Colorado Anschutz Medical Campus, 12801 E 17(th) Avenue, RC-1S, Aurora, CO 80045, USA.
Lynn SchuchterAbramson Cancer Center University of Pennsylvania, Philadelphia, PA 19104, USA.
Asier Unciti-BrocetaCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Valerie G BruntonCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
E Elizabeth PattonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK. Electronic address: e.patton@igmm.ed.ac.uk.
Edinburgh Cancer Research · GBMRC Institute of Genetics and Molecular Medicine · GBUniversity of Pennsylvania · USIndiana University School of MedicineStanford University · USWellcome Sanger Institute · GBUniversity of Colorado Anschutz Medical Campus · USUniversity of Edinburgh · GBWestern General Hospital · GB
Funding
Targeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MMECHANISMS OF ETHANOL-INDUCED CARDIAC PROTECTIONR01AA011147 · NIAAA · STANFORD UNIVERSITY · PI DARIA MOCHLY-ROSEN · 1996 to 2026
$8.2MMechanisms of Ethanol-Induced Cardiac ProtectionR37AA011147 · NIAAA · STANFORD UNIVERSITY · PI MOCHLY-ROSEN, DARIA · 2009 to 2018
$5.3MActivation and Inhibition of Aldehyde Dehydrogenase 2R01AA018123 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI HURLEY, THOMAS D. · 2009 to 2013
$2.0MModulation of Inflammasome-mediated cytokine activation by EGCG in human melanomaR01CA197919 · NCI · UNIVERSITY OF COLORADO DENVER · PI FUJITA, MAYUMI · 2016 to 2020
$1.9MIsozyme-selective ALDH Inhibitors for Sensitizing Ovarian Cancer Stem-like Cells to ChemotherapyR01CA214567 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BUCKANOVICH, RONALD J, LARSEN, SCOTT D · 2017 to 2019
$1.8MTargeting Ovarian Cancer Stem Cells Through Selective Inhibition of ALDH1A1R21CA198409 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI HURLEY, THOMAS D., MATEI, DANIELA E · 2015 to 2016
$373kAutoinflammation in Human MelanomaI01BX001228 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI FUJITA, MAYUMI · 2012 to 2022
–BLRD VA I01 BX001228Cancer Research UK C157/A24837Medical Research Council MC_PC_U127585840Medical Research Council MC_UU_00007/9NCI NIH HHS P50 CA174523NCI NIH HHS R01 CA197919NCI NIH HHS R01 CA214567NCI NIH HHS R21 CA198409NIAAA NIH HHS R01 AA011147NIAAA NIH HHS R01 AA018123NIAAA NIH HHS R37 AA011147Wellcome TrustWellcome Trust 101527/Z/13/Z
Abstract
5-Nitrofurans are antibiotic pro-drugs that have potential as cancer therapeutics. Here, we show that 5-nitrofurans can be bio-activated by aldehyde dehydrogenase (ALDH) 1A1/1A3 enzymes that are highly expressed in a subpopulation of cancer-initiating (stem) cells. We discover that the 5-nitrofuran, nifuroxazide, is selective for bio-activation by ALDH1 isoforms over ALDH2, whereby it both oxidizes ALDH1 and is converted to cytotoxic metabolites in a two-hit pro-drug mechanism. We show that ALDH1
Indexed as
Aldehyde Dehydrogenase 1 FamilyAnimalsAntineoplastic AgentsCell Line, TumorHydroxybenzoatesIsoenzymesMelanomaMiceMolecular StructureNeoplastic Stem CellsNitrofuransProdrugsRetinal DehydrogenaseAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, mouseAntineoplastic AgentsHydroxybenzoatesIsoenzymesnifuroxazideNitrofuransProdrugsRetinal Dehydrogenase5-nitrofuransALDHBRAF inhibitorcancer stem cellsdrug mechanism of actiondrug targetsmelanomanifuroxazidepro-drugstumor-initiating cells
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