Tacrolimus

Tacrolimus is an immunosuppressive drug that binds FKBP12 and inhibits calcineurin, reducing T-cell activation. It is used to prevent organ-transplant rejection and, as a topical treatment, for inflammatory skin diseases such as atopic dermatitis.

FKBP12: FKBP12 is a cellular protein that binds tacrolimus and other ligands. Tacrolimus must bind FKBP12 before the complex can inhibit calcineurin.
Organ transplantation: Organ transplantation is the transfer of an organ from a donor to a recipient. Tacrolimus is widely used to reduce immune-mediated rejection of transplanted organs.
Therapeutic drug monitoring: Therapeutic drug monitoring uses measured drug concentrations to guide dosing and reduce harm or treatment failure. Tacrolimus has a narrow therapeutic range, so blood concentrations often guide systemic dosing.
Cyclosporine: Cyclosporine is an immunosuppressive drug that binds cyclophilin and inhibits calcineurin. It blocks the same enzyme as tacrolimus but uses a different binding protein.
Calcineurin: Calcineurin is a calcium- and calmodulin-dependent phosphatase that activates transcription factors including NFAT. The tacrolimus–FKBP12 complex inhibits this phosphatase, interrupting immune-cell signaling.
Atopic dermatitis: Atopic dermatitis is a chronic inflammatory skin disease marked by itching and recurring eczema. Topical tacrolimus treats inflammation without the skin atrophy associated with prolonged topical corticosteroid use.
Nephrotoxicity: Nephrotoxicity is kidney injury caused by a drug or other toxic exposure. Tacrolimus can impair kidney function, complicating care after transplantation.
Sirolimus: Sirolimus is an immunosuppressive drug that binds FKBP12 and inhibits mTOR. It shares tacrolimus's binding protein but acts downstream on a different target.
NFAT: NFAT is a family of transcription factors regulated by phosphorylation and dephosphorylation. Calcineurin inhibition keeps NFAT from activating genes involved in T-cell responses.
Topical calcineurin inhibitor: A topical calcineurin inhibitor is a skin-applied drug that suppresses local immune signaling by inhibiting calcineurin. Tacrolimus ointment is a topical calcineurin inhibitor used for inflammatory skin disease.

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