2015 Antineoplastics


Mechanisms of action

6-MERCAPTOPURINE and 6-THIOGUANINE must be activated by HGPRT to T‑IMP and 6‑thioGMP.  T-IMP and 6-thioGMP are poor substrates for guanylyl kinase, therefore IMP and GMP accumulate, causing “pseudofeedback inhibition” of purine nucleoside phosphorylase (PNP), PRPP glutamyl amidotransferase (the 1st committed steps in purine synthesis) and HGPRT (which is a key enzyme in the purine "salvage" pathway).
Critical Facts icon
  • these alterations result in :
    1. interference with DNA and RNA synthesis
    2. inhibition of purine nucleotide interconversion
    3. a decrease in intracellular levels of guanine nucleotides (inhibition of glycoprotein synthesis)
    4. incorporation of purinethiols into both DNA and RNA, leading to DNA damage

  • AZATHIOPRINE is converted to 6-MERCAPTOPURINE - used primarily as an immunosuppressant rather than an antineoplastic
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM