Mechanism for hMTH1's broad substrate specificity revealed
Human MutT homolog 1 (hMTH1) protein acts as the primary enzyme for breaking down (hydrolyzing) damaged (oxidized) deoxynucleoside triphosphates (dNTPs) the substrates of DNA synthesis. Recently, hMTH1 has drawn attention as a popular target for new anticancer therapies because it is non-essential for normal cells, but cancer cells require it to avoid incorporating oxidized nucleotides into DNA, which would result in cancer cell death. Now, hMTH1 inhibitors are developed as anticancer drug candidates. Even though some reports argue against the usefulness of hMTH1 inhibition, highly potent and selective inhibitors of hMTH1, which would allow for the introduction of oxidized nucleotides into cancer cell DNA, are expected for future cancer treatment.