FK-506

FK506 is 23-membered macrolide lactone discovered in 1984, by Kino T, Hatanaka H and Hashimoto M. [reference 2] FK506 exhibits potent inhibitory effect on T- lymphocyte activation. It binds to immunophilins FK506 binding proteins (FKBP-12) and a complex of FKBP-12, calcium, calmodulin and calcineurin is formed, inhibiting phosphatase activity of calcineurin. This prevents dephosphorylation and translocation of nuclear factor of activated T – cells (NF-AT) and inhibits transcription of early T-cell activation gene, Interleukin-2, Tumour Necrosis Factor (TNF-a) and proto-oncogenes; suppressing expression of IL-2 and IL-7 receptor. This results in inhibition of T-lymphocyte activation. FK506 also inhibits the mixed lymphocyte reaction, generation of cytotoxic T-cells and T-cell dependent B-cell activation.