New Immunosuppressants: Immunosuppression and Immunomodulation

Immunosuppressive therapy can be used to prevent graft rejection and to treat autoimmune diseases. Recent advances in the understanding of this immune response have focused on the development of new immunosuppressive medications and new approaches to induction of immunological tolerance and reduction of late graft losses. In this overview, preclinical and clinical studies of the new immunosuppressive agents and their analogs are reviewed from the discovery of cyclosporine. More recently, certain classical immunosuppressants tacrolimus and sirolimus were well used to prevent acute rejection of transplanted organs and to ensure long-term survival of the allografts. However, some immunosuppressants have specific and significant toxic effects, so that drug combination therapy has been of great interest in addition to the introduction of novel small molecule agents, including mycophenolate mofetil; sirolimus analogs, SDZ RAD; 15-deoxyspergualin (DSG) and its analogs, FTY720; malononitrilamide analogs, FK778 and leflunimide; Sanglifehrins A; PG490-88; FK330 and 4-amino-analog of tetrahydrobiopterin of nitric oxide synthase inhibitors; genistein, baohuoside- 1 and apigenin of flavonoid family; Prostaglandin E2; CYP3A4, CYP3A5, and P-glycoprotein; vitamin E analogs, α-tocopheryl (PEG-1000) succinate (TPGS). A newer immunomodulation concept and their new drugs will also be described.