Antimetabolite Chemotherapy

Aka: Antimetabolite Chemotherapy, Structural Analog Chemotherapy, Purine Analog, Antineoplastic Antimetabolite Purine Analog, Pyrimidine Analog, Cytidine Analog, Folic Acid Antagonist, Histone Deacetylase Inhibitor, HDAC Inhibitor

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II. Definitions

  1. Antimetabolite Chemotherapy
    1. Agents (typically analogs) that block DNA, RNA or Protein synthesis
    2. Suppress cancer cell expression, growth and replication

III. Medications Purine Analogs

  1. Mechanism
    1. Purine Analogs, resembling adenine or guanine, and incorporate into DNA
    2. Result in DNA cross-linking and inhibition of synthesis and repair of DNA
  2. Purine Analogs
    1. Azathioprine (Imuran)
    2. Cladribine (Leustatin)
    3. Clofarabine
    4. Fludarabine (Fludara)
    5. Mercaptopurine (6-MP, Purinethol)
    6. Nelarabine
    7. Pentostatin (Nipent)
    8. Thioguanine (6-TG)

IV. Medications: Pyrimidine Analogs

  1. Mechanism
    1. Pyrimidine Analogs, resembling cytosine, uracil or thymine, and incorporate into DNA and RNA
    2. Inhibits DNA and RNA synthesis
    3. Cytidine Analogs are described in a separate category below
  2. Pyrimidine Analogs
    1. Capecitabine (Xeloda)
    2. Floxuridine
    3. Fluorouracil (5-FU)
    4. Trifluridine

V. Medications: Cytidine Analogs

  1. Mechanism
    1. Antineoplastic, PyrimidineNucleoside analogs of cytidine
    2. By binding DNA at cytidine binding sites, these analogs block DNA methyltransferase, and in turn DNA methylation
  2. Cytidine Analogs
    1. Azacitidine (5-azacytidine)
    2. Cytarabine (cytosine arabinoside, ara-C)
    3. Decitabine
    4. Gemcitabine

VI. Medications: Folic Acid Antagonist

  1. Mechanism
    1. Folic Acid analogs that resemble its structure, binding Folate-dependent enzymes, and block their activity
    2. As an example, inhibition of dihydrofolate reductase results in a failed synthesis of Tetrahydrofolate (FH4)
    3. Result in decreased DNA, RNA and Protein synthesis
  2. Folic Acid Antagonists
    1. Methotrexate
    2. Pemetrexed
    3. Pralatrexate

VII. Medications: Histone Deacetylase Inhibitor (HDAC Inhibitor)

  1. Mechanism
    1. Histones are the spools around which DNA are wrapped, and which play a role in gene expression
      1. Cancers may be facilitated by abnormally expressed genes in specific histone regions
    2. HDAC Inhibitors block histone deacetylase
      1. Histone deacetylase is an enzyme that catalyzes removal of acetyl groups from core histones
      2. Results in hyperacetylation of histones, suppressing gene expression and cell differentiation
  2. HDAC Inhibitors
    1. Belinostat (Beleodaq)
    2. Romidepsin (Istodax)
    3. Panobinostat (Farydak)
    4. Vorinostat (Zolinza)

VIII. Medications: Miscellaneous

  1. Various mechanisms that interfere with DNA, RNA or Protein synthesis
  2. Agents
    1. Hydroxyurea

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