FK-506 (Tacrolimus)

Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection. It reduces interleukin-2 (IL-2) production by T-cells. It is also used in a topical preparation in the treatment of severe atopic dermatitis (eczema), severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus is chemically known as a macrolide. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear factor of activated T-cells), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[5] In detail, Tacrolimus reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.[6] Although this activity is similar to cyclosporin, studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporin.[7] Although short-term immunosuppression concerning patient and graft survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid profile, and this may have important long-term implications given the prognostic influence of rejection on graft survival.[8] Specific Rotation: 75.0-90.0 Total Impurities: (same/less than)2.0% Water: (same/less than)3.0% Residue on ignition: (same/less than)0.1% Storage and Stability: May be stored at RT for short-term only. Long-term storage is recommended at -20 degrees C. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Toxicity and Hazards: Due to the potential danger associated with the use of some of United States Biological biochemicals, all products should be handled by qualified personnel only, trained in laboratory procedures, and familiar with potential hazards. Information is not available on the possible hazards of many experimental compounds. The absence of a warning must not be interpreted as indication of safety. The ultimate responsibility for the proper handling of any and all chemicals lies with the user. All goods sold by United States Biological carry the condition that liability for any injury, loss or damage whatsoever to persons or real property resulting from the handling of the said goods lies with the user. Acceptance of our goods binds the customer to these terms.