Nudix hydrolase 1 is an enzyme that belongs to the Nudix hydrolase superfamily, characterized by the conserved Nudix motif that forms the catalytic center for nucleotide diphosphate hydrolysis. These enzymes remove toxic and mutagenic nucleotide derivatives from the cell, such as oxidized nucleotides, protecting genomic integrity. Nudix hydrolase 1 displays substrate specificity for oxidized nucleotides (e.g., 8-oxo-dGTP) and plays a role in folate biosynthesis in bacteria. It is found in the cytosol of both plant and animal cells and has implications in cancer, infection, and oxidative stress-related diseases.
Other names
NUDX1MutT homolog 1 (in humans often called MTH1)Dihydroneopterin triphosphate pyrophosphataseNudix NTP hydrolase
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Mechanism of action
Drugs typically inhibit the hydrolase activity, leading to accumulation of mutagenic nucleotides and enhanced cancer cell death
Modulation of cellular nucleotide pools
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Biological functions
Metabolism of nucleotide diphosphate derivativesDetoxification of potentially mutagenic nucleotide species (e.g., 8-oxo-dGTP)Maintenance of genomic stabilityRegulation of signaling molecule levelsFolate biosynthesis (in some species)
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Disease associations
Cancer (NUDIX hydrolases have altered expression in various cancers and are being explored as cancer targets)Oxidative stress-related diseasesBacterial infection (targets for antibacterial drug development)Genetic disorders related to DNA damage response
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Safety considerations
Potential off-target effects due to broad substrate specificityRisk of genomic instability if hydrolase function is excessively inhibitedPossible impact on normal cell DNA repair and metabolism
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Interacting drugs
Small molecule inhibitors of MTH1 (MutT homolog 1) used in research and preclinical studies
1 more in the full profile.
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Biomarkers
Levels of oxidized nucleotides (e.g., 8-oxo-dGTP) for efficacy monitoringNUDX1/MTH1 expression or activity in tissues (being investigated in cancer research)
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