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Cyclophilin inhibitors and ligands target cyclophilins, prolyl isomerases that bind cyclosporin A. Cyclophilin was identified in 1984 as the cytosolic protein that binds this immunosuppressant. In 1991 the cyclophilin and cyclosporin A complex was shown to inhibit the phosphatase calcineurin, which explains the immunosuppressive action. Alisporivir and NIM811 are cyclosporin analogs that bind cyclophilins but do not inhibit calcineurin. Cyclosporin C is a natural member of the cyclosporin family, and Cyclophilin inhibitor 1 is described as a cyclophilin A inhibitor. The set also includes RAS inhibitors such as RMC-7977 and elironrasib. These compounds form a tri-complex with cyclophilin A and active RAS, a mechanism reported in 2023.
