mTOR and FTY 720 inhibitors

SIROLIMUS: The leading member of the mTOR inhibitor family, sirolimus or rapamycin, has dose-dependent side effects that can generally be well controlled. Sirolimus can be combined with tacrolimus at therapeutic doses; likewise for the sirolimus-cyclosporine combination at moderate dosage. Effective plasma concentrations of sirolimus vary from 5 to 20 ng/ml depending on the combination of immunosuppressant agents used. Sirolimus has been shown to inhibit metastatic diffusion of renal adenocarcinoma in the mouse. Its complex side effects on angiogenesis, fibrosis processes and chronic rejection are still being investigated. EVEROLIMUS: Everolimus, or RAD, has a very short half-life, but induces fewer hematologic effects. The therapeutic dose must reach at least 3 ng/ml to prevent rejection. Doses above 15 ng/ml increase the risk of thrombocytopenia. FTY 720: A new immunosuppressant agent, FTY 720, does not belong to any known family. It has a totally different mechanism of action compared with currently available immunosuppressants. FTY 720 increases the expression of chemokine receptors on the surface of T cells making them unavailable for the rejection reaction. FTY 720 has a very long half-life (108 hours). Due to its particular liver metabolism, there is a very low risk of drug interactions.