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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.
MTH1 Ligand 1 is a specific ligand that targets the MTH1 protein, playing a crucial role in cellular pathways associated with nucleotide metabolism and cancer cell survival. This compound is instrumental in the synthesis of PROTAC aTAG 2139, facilitating targeted protein degradation in research applications. Its selectivity for MTH1 makes it a valuable tool for investigating therapeutic strategies aimed at mitigating oncogenic processes.
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