Tacrolimus, known as FK506, is a macrolide immunosuppressant produced by
Streptomyces tsukubaensis. Tacrolimus is practically insoluble in water, freely soluble in ethanol and DMF, and very soluble in methanol and chloroform. Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that tacrolimus is inactive by itself and requires binding to an intracellular protein, FK506 binding protein-12 (FKBP-12), for activation in cells. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin (a calcium and calmodulin dependent protein phosphatase) is then formed and the phosphatase activity of calcineurin inhibited. This effect may prevent both T-lymphocyte signal transduction and IL-2 transcription. Cyclosporin A [
C2408] also inhibits calcineurin but is less potent than tacrolimus. Tacrolimus is mainly metabolized by cytochrome P 450 IIIA (CYP3A) subfamilies. (The product is for research purpose only.)