SDZ RAD, A NEW RAPAMYCIN DERIVATIVE: Pharmacological Properties In Vitro and In Vivo

摘要: Background. This report describes the preclinical pharmacological profile of new rapamycin analog, SDZ RAD, i.e., 40-O-(2-hydroxyethyl)-rapamycin. Methods. The effects RAD were assessed in a variety vitro and vivo models, which included an autoimmune disease model as well kidney heart allotransplantation models using different rat strain combinations. Results. has mode action that is from cyclosporine or FK606. In contrast to latter, inhibits growth factor-driven cell proliferation general, demonstrated for lymphoid line vascular smooth muscle cells. immunosuppressive by inhibition mouse human mixed lymphocyte reactions antigen-driven T-cell clones. concentrations needed achieve 50% all these assays fall into subnanomolar range. effective when given oral route doses ranging between 1 mg/kg/day 5 mg/kg/day. When compared with rapamycin, activity generally about two three times lower; however, administered orally, at least active rapamycin. Conclusions. conclusion, new, orally rapamycin-derivative efficiently prevents graft rejection allotransplantation. therefore been selected development use combination A prevent acute chronic after solid organ