ArticleCancer research2021
MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.
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Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 29 citations in OpenAlex.
- The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy.International urology and nephrology · 2026Article
- MTH1 in the disorders of the central nervous system: scope beyond brain tumors and challenges.Acta neurologica Belgica · 2025Review
- Neutron and time-resolved X-ray crystallography reveal the substrate recognition and catalytic mechanism of human Nudix hydrolase MTH1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025Review
- Pharmacological inhibition of MutT homolog 1 (MTH1) in allergic airway inflammation as a novel treatment strategy.Respiratory research · 2025Article
- CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma.Nature communications · 2024Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Mitotic MTH1 inhibitor TH1579 induces PD-L1 expression and inflammatory response through the cGAS-STING pathway.Oncogenesis · 2024Article
- Oxidative stress is two-sided in the treatment of acute myeloid leukemia.Cancer medicine · 2024Review
- Role of reactive oxygen species in myelodysplastic syndromes.Cellular & molecular biology letters · 2024Review
- Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA-24 with Tumor-Selective Toxicity.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option.Frontiers in cell and developmental biology · 2024Review
- Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.Science advances · 2023Article
- GNF-7, a novel FLT3 inhibitor, overcomes drug resistance for the treatment of FLT3‑ITD acute myeloid leukemia.Cancer cell international · 2023Article
- Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.Molecules (Basel, Switzerland) · 2023Article
- Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023Article
- Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia.Frontiers in oncology · 2023Review
- OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.Frontiers in cell and developmental biology · 2023Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic Spindle.Cancers · 2021Article
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Authors and funding
32 authors at 6 institutions in 5 countries.
Kumar Sanjiv *Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
José Manuel Calderón-Montaño *Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6845-797X
Therese M PhamScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Tom ErkersScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Viktoriia TsuberScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Ingrid AlmlöfScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Andreas HöglundScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Yaser HeshmatiCenter for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Brinton Seashore-LudlowScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8658-5967
Akhilesh Nagesh DandaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Helge GadScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6530-1443
Elisee WiitaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Camilla GöktürkScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-6272-9927
Azita RastiScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Stefanie FriedrichScience for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0000-0002-3889-5589
Anders CentioThe Finsen Laboratory, Rigshospitalet/National University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Montserrat EstruchThe Finsen Laboratory, Rigshospitalet/National University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-7162-4158
Thea Kristin VåtsveenDepartment for Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Nona StruyfScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-6975-0753
Torkild VisnesScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1047-988X
Martin ScobieScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Tobias KoolmeisterScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Martin HenrikssonScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Olov WallnerScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Teresa SandvallScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Sören LehmannCenter for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Kim Theilgaard-MönchThe Finsen Laboratory, Rigshospitalet/National University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-4239-4939
Mathew J GarnettWellcome Sanger Institute, Cambridge, United Kingdom.ORCID 0000-0002-2618-4237
Päivi ÖstlingScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Julian WalfridssonCenter for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Thomas HelledayScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Ulrika Warpman BerglundScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. ulrika.warpmanberglund@scilifelab.se ulrika.warpmanberglund@oxcia.com.ORCID 0000-0002-6372-1396
Science for Life Laboratory · SEUniversity of Copenhagen · DKKarolinska University Hospital · SEOslo University Hospital · NOUppsala University · SEWellcome Sanger Institute · GB
Funding
Wellcome Trust 206194
Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine
Indexed as
MitosisAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBlast CrisisCell ProliferationCytarabineDNA Repair EnzymesDoxorubicinFemaleGene Expression Regulation, LeukemicHumansLeukemia, Myeloid, AcuteMiceMice, Inbred NODMice, SCID8-oxodGTPaseCytarabineDNA Repair EnzymesDoxorubicinkaronudibPhosphoric Monoester HydrolasesPyrimidinesReactive Oxygen Species
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