Prograf is the generic name for the macrolide immunosuppressant previously known by its experimental name FK506. Prograf was first discovered while screening for antibacterial activity of a multitude of compounds. This macrolide is produced by Streptomyces tsukabaensis, a bacterium found in the soil near Tsukuba, Japan. The mechanism of action of Prograf is closely related to that of cyclosporine. However, while Prograf binds tightly to the cellular protein named FKBP (FK506-binding protein) 12, cyclosporine binds cyclophilin. The target of either drug/intracellular receptor complex is a calcium-activated phosphatase called calcineurin, which is required for many functions in a variety of tissues: learning and memory, renal function, and immune responses. The selective sensitivity of immune function to these drugs has two reasons: 1. the low level of expression of calcineurin in lymphocytes relative to cells in other tissues; 2. an absolute requirement for calcineurin in immune activation. During antigen specific T-cell activation intracellular calcium is released and calcineurin is activated to dephosphorylate its target proteins including the transcription factor NFAT (nuclear factor of activated T cells). Upon dephosphorylation, NFAT translocates to the nucleus, where it binds its nuclear counterpart to form an active transcription factor inducing the production of several cytokines mandatory for initiating an immune response. Hence, calcineurin inhibitors interfere with antigen specific T-cell activation. Furthermore, Prograf affects the function of mast cells, basophile leucocytes and Langerhans cells. These characteristics explain the great interest to apply Prograf topically on inflamed skin, particularly since it was the first new topical immune suppressant since the introduction of steroids. The first successful use of topical Prograf in patients with atopic dermatitis was reported by Nakagawa et al. in 1994 and already 6 years later the U.S. Food and Drug Administration (FDA) approved Prograf ointment as a promising treatment for atopic dermatitis. Additionally, Prograf was investigated for a wide variety of inflammatory skin diseases beyond atopic dermatitis; particularly for conditions recalcitrant to other forms of therapy.
Other names for this medication:
Tacrolimus,
Advagraf,
Envarsus,
Prograf,
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