Therapeutic Applications of Purine and Pyrimidine Metabolism By Brian Kim and Jessica Swavely

Mechanisms of Action

1) Synthetic Nucleotide Analog

2) Cofactor Analog or Competitor

3) Folate Analog

What Pathway Do I Affect?

1) Folate Cycle (Affects both purine and pyrimidine synthesis)

2) Pyrimidine Synthesis

3) Purine Synthesis

Methotrexate and Aminopterin

Treatment for: acute lymphoblastic leukemia, non-Hodgkin's lymphoma, osteosarcoma, and colon cancer and acute lymphoblastic leukemia, psoriasis, respectively

Methotrexate is also used in severe psoraisis, Crohn's disease, and rheumatoid arthritis

Sulfamethoxazole/Trimethoprim (Bactrim or Septra)

Treatment for: UTI, middle ear infections, bronchitis, Traveler's diarrhea, and shigellosis

Allopurinol (Zyloprim)

Treatment for: gout, kidney stones, and management of Lesch-Nyhan Syndrome


Treatment for: cancer

Primarily an inhibitor of thymidylate synthase

Creates FdUMP, FdUTP and FUTP

Capecitabine (Xeloda)

Transformed to 5-fluorouracil in vivo

Works to inhibit thymidylate synthase

Treatment for: colon cancer, metastatic breast and colorectal cancer

Vistoguard (Uridine Triacetate)

5-fluorouracil overdose (prodrug)

Deacetylated via nonspecific esterases

Competitively inhibits 5-FU induced cell death

Treatment for hereditary orotic acidemia and 5-Fluorouracil overdose


Treatment as an antibiotic

Glutamine analog

Blocks VI synthase (5th step in inosine monophosphate synthesis)


Treatment for: acute lymphoblastic leukemia, Crohn's disease, and ulcerative colitis

Competes with purine derivatives (hypoxanthine and guanine) for hypoxanthine-guanine phosphoribosyltransferase

Converted to thio inosine monophosphate (TIMP) – inhibits IMP-dependent reactions


Treatment for: tentative chemotherapy drug

Competitively inhibits glutamate-dependent enzymes

Created By
Jessica Swavely

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