ArticleScientific reports2016
Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 99 citations in OpenAlex.
- Article
- 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
- Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.Nature communications · 2024Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Identification of a dihydroorotate dehydrogenase inhibitor that inhibits cancer cell growth by proteomic profiling.Oncology research · 2023Article
- OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.Frontiers in cell and developmental biology · 2023Article
- Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023Article
- Overexpressed c-Myc Sensitizes Cells to TH1579, a Mitotic Arrest and Oxidative DNA Damage Inducer.Biomolecules · 2022Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases.Basic & clinical pharmacology & toxicology · 2022Review
- 1Molecules (Basel, Switzerland) · 2022Review
- Image-Based Annotation of Chemogenomic Libraries for Phenotypic Screening.Molecules (Basel, Switzerland) · 2022Article
- Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress.Oncogene · 2022Article
- NUDT1 Could Be a Prognostic Biomarker and Correlated with Immune Infiltration in Clear Cell Renal Cell Carcinoma.Applied bionics and biomechanics · 2022Article
- TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic Spindle.Cancers · 2021Article
- MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.Cancer research · 2021Article
- Total synthesis of biselide A.Chemical science · 2021Article
- Development of MTH1-Binding Nucleotide Analogs Based on 7,8-Dihalogenated 7-Deaza-dG Derivatives.International journal of molecular sciences · 2021Article
- Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration-resistant prostate cancer.Oncology letters · 2021Article
- Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.Acta pharmaceutica Sinica. B · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since recent publications suggested that the survival of cancer cells depends on MTH1 to avoid incorporation of oxidized nucleotides into the cellular DNA, MTH1 has attracted attention as a potential cancer therapeutic target. In this study, we identified new purine-based MTH1 inhibitors by chemical array screening. However, although the MTH1 inhibitors identified in this study targeted cellular MTH1, they exhibited only weak cytotoxicity against cancer cells compared to recently reported first-in-class inhibitors. We performed proteomic profiling to investigate the modes of action by which chemically distinct MTH1 inhibitors induce cancer cell death, and found mechanistic differences among the first-in-class MTH1 inhibitors. In particular, we identified tubulin as the primary target of TH287 and TH588 responsible for the antitumor effects despite the nanomolar MTH1-inhibitory activity in vitro. Furthermore, overexpression of MTH1 did not rescue cells from MTH1 inhibitor-induced cell death, and siRNA-mediated knockdown of MTH1 did not suppress cancer cell growth. Taken together, we conclude that the cytotoxicity of MTH1 inhibitors is attributable to off-target effects and that MTH1 is not essential for cancer cell survival.
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