Target intelligence / Profile preview

De novo purine synthesis enzymes and nucleic acids (DNPS)

Target
DNPS
Molecular classification
Enzyme, Nucleic acid, Metabolic pathway
01

Overview

The de novo purine synthesis pathway is a multi-step enzymatic process that constructs purine nucleotides, such as adenosine monophosphate (AMP) and guanosine monophosphate (GMP), from simple precursor molecules like phosphoribosyl pyrophosphate (PRPP), amino acids, and carbon dioxide. This pathway is essential for providing the building blocks required for DNA replication and RNA transcription, particularly in rapidly dividing cells such as cancer cells and activated lymphocytes. Key enzymes in this pathway, including inosine monophosphate dehydrogenase (IMPDH) and phosphoribosylpyrophosphate amidotransferase (PPAT), serve as critical regulatory points. Therapeutic intervention often involves the use of antimetabolites or enzyme inhibitors that disrupt nucleotide pools, thereby inhibiting cell proliferation and inducing apoptosis. Because of its central role in cellular growth, this pathway is a primary target for chemotherapy, immunosuppressive therapy, and antiviral treatments.

Other names
Purine biosynthetic pathwayDe novo purine nucleotide biosynthetic pathwayPurine metabolismPurinosome
02

Mechanism of action

Inhibition of rate-limiting enzymes (e.g., IMPDH, PPAT) or incorporation of antimetabolites into DNA/RNA to induce chain termination or mutagenesis.

03

Biological functions

Nucleotide biosynthesisDNA replicationRNA transcriptionCell proliferationEnergy metabolism
04

Disease associations

CancerAutoimmune diseaseInflammationInfectionGout
05

Safety considerations

MyelosuppressionHepatotoxicityImmunosuppression-related infectionsGastrointestinal toxicityTeratogenicity
06

Interacting drugs

Methotrexate

9 more in the full profile.

07

Biomarkers

Thiopurine methyltransferase (TPMT) activityNUDT15 genotypeIntracellular 6-TGN levelsHypoxanthine-guanine phosphoribosyltransferase (HGPRT) levels

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