Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide

Curr Opin Immunol. 1996 Oct;8(5):710-20. doi: 10.1016/s0952-7915(96)80090-2.


Among all the new immunosuppressive molecules being investigated either preclinically or clinically, four stand out: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide (and its malononitriloamide analogs). Each drug has distinct mechanisms of immunosuppressive action, and in the past year significant advances have been made in our understanding of the actions of these drugs at the molecular and even atomic levels. Data from recent clinical trials demonstrate that these drugs very effectively suppress graft rejection or autoimmune diseases, validating the pivotal role played by each of their distinct molecular targets in the normal functioning of immune cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Graft Rejection / drug therapy
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / toxicity
  • Isoxazoles / pharmacology
  • Leflunomide
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Polyenes / pharmacology
  • Pyrimidine Nucleotides / biosynthesis
  • Sirolimus
  • Tacrolimus / pharmacology
  • Xenobiotics / pharmacology*
  • Xenobiotics / toxicity


  • Immunosuppressive Agents
  • Isoxazoles
  • Polyenes
  • Pyrimidine Nucleotides
  • Xenobiotics
  • Leflunomide
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus