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Showing 1–11 of 11 results
Advanced filters: Author: Ann-Sofie Jemth Clear advanced filters

  • Dysfunctional redox regulation in cancer can damage dNTPs so inhibiting dNTP pool sanitizing enzymes, such as MTH1, is a potential cancer treatment. Here, Carter et al.characterize MTH2 (NUDT15) and show that it is not a dNTP sanitizer, and so is unlikely to influence the efficacy of MTH1 inhibitors.

    • Megan Carter
    • Ann-Sofie Jemth
    • Pål Stenmark
    ResearchOpen Access
    Nature Communications
    Volume: 6, P: 1-10

  • In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.

    • Helge Gad
    • Tobias Koolmeister
    • Thomas Helleday
    Research
    Nature
    Volume: 508, P: 215-221

  • In this study, Green, Marttila, Kiweler et al. characterize one-carbon metabolism rewiring in response to a dual MTHFD1 and MTHFD2 inhibitor. This work provides insight into one-carbon fluxes, and reveals a previously uncharacterized vulnerability in cancer cells created by folate trapping.

    • Alanna C. Green
    • Petra Marttila
    • Johannes Meiser
    ResearchOpen Access
    Nature Metabolism
    Volume: 5, P: 642-659

  • TH1760 is a first-in-class, potent, selective and cell-active inhibitor against human NUDT15, which sensitizes cells to 6-thioguanine treatment. TH1760 represents a valuable tool for deciphering the enigmatic functions of NUDT15.

    • Si Min Zhang
    • Matthieu Desroses
    • Thomas Helleday
    Research
    Nature Chemical Biology
    Volume: 16, P: 1120-1128

  • A chemoproteomic screen is used here to identify MTH1 as the target of SCH51344, an experimental RAS-dependent cancer drug; a further search for inhibitors revealed (S)-crizotinib as a potent MTH1 antagonist, which suppresses tumour growth in animal models of colon cancer, and could be part of a new class of anticancer drugs.

    • Kilian V. M. Huber
    • Eidarus Salah
    • Giulio Superti-Furga
    Research
    Nature
    Volume: 508, P: 222-227

  • The NUDIX hydrolases are known to be involved in several cellular processes and diseases, such as cancer, but remain poorly characterized as a family. Here, the authors provide a comprehensive analysis of the structural, biochemical, and expression properties of 18 human NUDIX proteins, and begin to address their functional inter-relationships.

    • Jordi Carreras-Puigvert
    • Marinka Zitnik
    • Thomas Helleday
    ResearchOpen Access
    Nature Communications
    Volume: 8, P: 1-17

  • NUDIX hydrolases are an important family of nucleotide-metabolizing enzymes. Here, the authors identify potent, small molecule inhibitors of NUDT5, which is implicated in ADP-ribose and 8-oxo-guanine metabolism, and confirm its role in gene regulation and proliferation in breast cancer cells.

    • Brent D. G. Page
    • Nicholas C. K. Valerie
    • Thomas Helleday
    ResearchOpen Access
    Nature Communications
    Volume: 9, P: 1-14