Comparison of FK‐506, Rapamycin, Ascomycin, and Cyclosporine in Mouse Models of Host‐versus‐Graft Disease and Heterotopic Heart Transplantation

Discovery of the potent immunosuppressive macrolactam, FK-506,' led to an appreciation of similar activity shared by ascomycin2 (also called FR-9005203), whose structure differs only by having an ethyl rather than ally1 group at position 21, and rapamycin: which is structurally related but mechanistically distinct.These compounds, like cyclosporine, all appear to act by inhibiting early events in cell proliferation and will inhibit the popliteal lymph node (PLN) response to allogeneic challenge, an in PiPo assay of lymph~proliferation.~~~The feasibility of semisynthetic modification for compound improvement spurred the need for simple assays to quantitatively compare numerous analogues.To examine the PLN for this purpose, we tested these compounds side by side in dose-response fashion and also compared them in a modified ear-heart transplant model.