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The chemical biology of immunophilin ligands.

The immunophilin ligands cyclosporin A, FK506 and rapamycin are best known for their immunosuppressive properties and their clinical use in transplantation medicine. These compounds or their analogs are also clinically used or investigated in various types of cancer, coronary angioplasty, dermatology, hepatitis C infections, and neuroprotection. Furthermore, the role of immunophilins in various pathologies is increasingly being recognized, supporting the preclinical drug development for novel immunophilin targets. Finally, immunophilin ligands are widely used as sophisticated tools in chemical biology. This review shows the progress on three major areas made in the last five years. An update of the immunosuppressive ligands and their clinical applications is discussed in the first part of the review, followed by a discussion about the emerging immunophilin targets and their respective ligands. The final section gives a detailed assessment of immunophilin ligand-based tools.