TH588

TH588 is a small molecule originally identified as a first-in-class inhibitor of Human MutT homolog 1 (MTH1), an enzyme that sanitizes oxidized nucleotide pools (such as 8-oxo-dGTP) to prevent their incorporation into DNA. By inhibiting MTH1, TH588 was designed to induce DNA damage and apoptosis specifically in cancer cells, which often operate under high oxidative stress. However, research has indicated that TH588 also exerts potent anti-tumor effects through MTH1-independent pathways, including the induction of reactive oxygen species (ROS) and microtubule-targeting activity. It has been studied preclinically in various malignancies, including melanoma and glioblastoma, as a potential antineoplastic agent.