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  • Title: [Inhibitors of NFAT-calcineurin pathway].
    Author: Miyatake S, Kaminuma O.
    Journal: Nihon Rinsho; 2005 Sep; 63(9):1633-9. PubMed ID: 16164223.
    Abstract:
    Cyclosporin A(CsA) and tacrolimus (FK506) are important immunosuppressants to inhibit rejection of transplanted organs and to treat various immunological disorders, however those drugs produce major side effects. Those drugs form complexes with cellular proteins, immunophilins (cyclophilin for CsA and FKBP for tacrolimus) and inhibit Ca-calmodulin dependent phosphatase calcineurin through direct binding. Calcineurin dephosphorylates various substrates including NFAT family proteins required for the expression of immunoregulatory molecules especially cytokines. NFAT-calcineurin pathway offers a good model system to apply new technology to develop drugs. Enzyme-substrate interaction could be an important target to develop drugs with high specificity accompanied with less side effects.
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