Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide.
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.
Transplantation Immunology Department of Cardiothoracic Surgery, North Stanford University, School of Medicine, CA 94305-5247, USA.
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Brazelton
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Morris
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D015262:Xenobiotics / Q000494:pharmacology* / Q000633:toxicity
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D011090:Polyenes; D011742:Pyrimidine Nucleotides; D015262:Xenobiotics; D000077339:Leflunomide; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus