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MTH1

MTH1 inhibitors and degraders target nudix hydrolase 1 (NUDT1, also called MTH1), which removes oxidized nucleotides. MTH1 hydrolyzes oxidized precursors such as 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dGTP), which keeps them out of newly synthesized DNA. In 2014 TH588 and TH287 were introduced as MTH1 inhibitors that increase oxidative damage in cancer cell DNA. A second 2014 study showed that (S)-crizotinib, the enantiomer of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib, binds MTH1 stereospecifically. Later selective inhibitors such as BAY-707 and IACS-4619 were used to reexamine whether MTH1 inhibition alone reduces cancer cell survival. SU0383 inhibits both MTH1 and 8-oxoguanine DNA glycosylase 1 (OGG1). aTAG 4531 and aTAG 2139 are MTH1-binding degraders used to remove MTH1-tagged fusion proteins in targeted degradation studies.

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  • 8-Oxo-dGTP
    Cat. No.
    A39260
    CAS No.
    139307-94-1

    8-Oxo-dGTP

    Synonyms: 8-Oxo-Deoxyguanosine triphosphate

    8-Oxo-dGTP (8-Oxo-Deoxyguanosine triphosphate) is a reactive oxidized guanine nucleotide that serves as a substrate for MTH1 and other pyrophosphohydrolases. This compound is known to act as a mutagen, integrating into DNA and leading to A:T to C:G transversions, which can contribute to genomic instability. Additionally, 8-Oxo-dGTP can provoke oxidative DNA modifications, strand breaks, and the promotion of apoptosis, particularly in mth1-deficient organisms. Its accumulation is linked to various biological processes and is extensively utilized in research on carcinogenesis, neurodegenerative diseases, and other pathologies.

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