2015 Antineoplastics

II. INHIBITORS OF DNA SYNTHESIZING ENZYMES:
CLADRIBINE, CYTARABINE (ARA-C), FLUDARABINE, GEMCITABINE

Types

  1. Antimetabolites:
    • PYRIMIDINES: CYTARABINE, GEMCITABINE (converted into compounds that compete with/mimic CDP and CTP)
    • PURINE: CLADRIBINE, FLUDARABINE (converted into compounds that compete with/mimic ADP and ATP)
    • incorporated into DNA where they block DNA polymerases (α = DNA synthesis and β = DNA repair)
    • also inhibit ribonucleotide reductase

  2. HYDROXYUREA
    • inhibits ribonucleotide reductase
    • synchronizes cells in a radiation-sensitive phase of the cell cycle (G1)
    • also used to treat sickle cell anemia, where it increases production of fetal hemoglobin γ, interfering with the polymerization of HbS, and therefore decreasing painful crises in patients with severe sickle cell disease
      • the mechanism whereby it increases fetal hemoglobin γ is unknown
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 4-may-15 9:25 PM