7,8-dihydro-8-oxoguanine triphosphatase mRNA (NUDT1 mRNA)

NUDT1, also known as MTH1 (MutT homolog 1), is a critical enzyme involved in the sanitization of the cellular nucleotide pool by hydrolyzing oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-dATP, into their corresponding monophosphates. This enzymatic activity prevents the incorporation of damaged nucleotides into DNA and RNA during replication and transcription, which would otherwise lead to transversion mutations, double-strand breaks, and genomic instability. In many cancer types, NUDT1 is significantly overexpressed to counteract the high levels of reactive oxygen species (ROS) generated by oncogenic signaling and rapid metabolic turnover. Consequently, NUDT1 has emerged as a promising therapeutic target, with small molecule inhibitors like Karonudib (TH1579) and RNA-targeting strategies such as siRNA being developed to induce selective DNA damage and apoptosis in malignant cells while sparing normal tissues. While initially considered a major metabolic vulnerability in cancer, the field continues to investigate the precise dependency of various tumor types on NUDT1 and the potential for off-target effects associated with its inhibition.

Other names

MTH1 mRNAMutT homolog 1 mRNA8-oxo-dGTPase mRNA7,8-dihydro-8-oxoguanine triphosphatase messenger RNA

Inhibition of MTH1 enzyme activity to prevent nucleotide pool sanitization and RNA interference-mediated degradation of NUDT1 mRNA to reduce protein expression.