Correlation of cyclosporine and metabolite binding to cyclophilin and a 50 kDa binding protein with in vitro immunosuppression: A preliminary report

Seven purified cyclosporine (CsA) metabolites were analyzed for binding to cyclophilin and to a 50 kDa protein purified from a JURKAT cell line. In addition, the potency of the seven metabolites, relative to CsA, was obtained using a primary mixed lymphocyte culture (MLC) suppression assay. CsA, M1, 17, and 21 were found to be immunosuppressive in the concentration range used (0–500 ng/mL). These results were then compared to protein binding. CsA and metabolite 17 (M17) bound to both proteins. Conversely, M1, 13, 21, and 26 bound only to cyclophilin, while M8 and M18 bound only to the 50 kDa protein.