Comparative activity of CP-17,193 and five established immunosuppressives toward the antigens SRBC and EL4.

A new immunosuppressant, 2-(4'-chlorophenyl)benzothiopyrano-(4,3-c)pyrazol-3-one, i.e. CP-17,193 was compared to several standard immunosuppressants with respect to its ability to depress immune responses to two antigens, EL4 tumour cells and sheep erythrocytes (SRBC). The order of suppressive potency on a weight basis was methotrexate greater than CP-17,193 greater than cyclophosphamide greater than 6-mercaptopurine greater than azathioprine greater than oxisuran for both antigens. In general, it took more immunosuppressant to inhibit the response to SRBC than to EL4. This resulted in a different therapeutic index for immunosuppression against each antigen. CP-17,193 and cyclophosphamide preferentially inhibited the humoral immune response and were the only agents demonstrating such selectivity. CP-17,193's favourable therapeutic index and its structural dissimilarity from the antimetabolite and alkylating immunosuppressants suggests that it may act through a novel mechanism.