Target intelligence / Profile preview

DNA synthesis and nucleotide metabolism pathway

Molecular classification
Enzyme, Metabolic pathway
01

Overview

DNA synthesis and nucleotide metabolism represent the collective biochemical processes required for the production of purine and pyrimidine nucleotides and their incorporation into DNA strands during replication. These pathways are essential for cell growth, division, and genomic maintenance, involving key enzymes such as dihydrofolate reductase (DHFR), thymidylate synthase (TS), and ribonucleotide reductase (RNR) (Source: StatPearls, 'Antimetabolites'). In clinical practice, these pathways are primary targets for antimetabolite chemotherapy and antiviral agents, which act as structural analogs to natural nucleotides or as enzyme inhibitors (Source: NIH, 'Nucleotide Metabolism'). By disrupting the availability of DNA building blocks, these drugs effectively halt the proliferation of malignant cells and pathogens. However, because these processes are also active in healthy, rapidly dividing cells, treatment often results in side effects such as bone marrow suppression and mucosal damage (Source: PubMed, 'Mechanisms of Antimetabolite Action').

Other names
Nucleotide biosynthesisDNA replication pathwayNucleic acid metabolismDe novo nucleotide synthesis
02

Mechanism of action

Inhibition of rate-limiting enzymes in the de novo or salvage pathways of nucleotide synthesis, leading to depletion of dNTP pools, DNA damage, and inhibition of DNA polymerase activity.

03

Biological functions

DNA replicationCell cycleCell proliferationDNA repair
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Disease associations

CancerInfectionAutoimmune diseaseInflammation
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Safety considerations

MyelosuppressionGastrointestinal toxicityMucositisAlopeciaTeratogenicityNephrotoxicity
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Interacting drugs

Methotrexate

7 more in the full profile.

07

Biomarkers

Ki-67Thymidylate synthase expression levelsDihydrofolate reductase levelsCirculating tumor DNA (ctDNA)

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