Target intelligence / Profile preview

Dihydrofolate Reductase (DHFR)

Target: DHFR
Molecular classification: Enzyme, Oxidoreductase

Overview

Dihydrofolate reductase (DHFR) is a key enzyme in folate metabolism that catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), essential for DNA synthesis, repair, and methylation. Inhibition of DHFR by drugs like methotrexate and trimethoprim is used in cancer therapy and as antibiotics. Genetic variations in DHFR can affect enzyme activity and drug response.

Mechanism of action

Inhibition of dihydrofolate reductase, blocking the conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting DNA synthesis and cell proliferation.

Biological functions

Folate metabolismNucleotide biosynthesisDNA synthesisDNA repairCell proliferation

Disease associations

CancerInfectionFolate deficiency related diseases (e.g., spina bifida)

Safety considerations

Drug resistance (e.g., via plasmid-borne DHFR variants)Patient sensitivity/resistance to antifolate drugs due to genetic variationsSide effects associated with antifolate drugs

Interacting drugs

Methotrexate

1 more in the full profile.

Biomarkers

DHFR expression levelsDHFR genetic polymorphisms (e.g., promoter polymorphisms, 19-bp deletion)

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