TH588

TH588 is a first-in-class nudix hydrolase family inhibitor.1 MTH1/NUDT1 is a family member that “sanitizes” oxidized deoxynucleotide triphosphates (dNTP) preventing their incorporation into DNA and thus avoiding DNA damage and cell death. TH588 inhibits MTH1/NUDT1 (IC50 = 5 nM) leading to cell death in several cancer cell lines while not affecting normal cells. Active in vitro and in vivo. Recent evidence has raised doubts about the cancer-killing ability of MTH1 inhibition.2,3