the Drug Monitor - Tacrolimus (Prograph)(FK-506) - Nasr Anaizi, PhD Tacrolimus is a macrolide of fungal origin (produced by Streptomyces Tsukubaenis) with strong immunosupressive actions. Its primary target appears to be the helper T lymphocytes, with little effect on other aspects of the immune response. However, because it acts early in the process of T cell activation, it has secondary effects on other cell types that are normally activated by factors produced by the T cells. The current model for the mechanism of action of tacrolimus (or cyclosporine) suggests that, in the T-cell cytoplasm, tacrolimus binds to a specific binding protein called immunophilin which is actually a cis-trans isomerase. The tacro-immunophilin complex in turn binds to and blocks a phosphatase called calcineurin. The latter is required for the translocation of an activation factor (NF-ATc) from the cytosol to the nucleus, where it would normally bind to and activate enhancers/promotors of certain genes.
