Cyclosporin A analogues: recent advances

Abstract

Cyclosporin A (Sandimmune^®, Neoral^®; Novartis) is a cyclic hydrophobic undecapeptide used to prevent and treat organ transplantation rejection. Cyclosporin A has potential therapeutic applications in the treatment of diseases such as asthma, psoriasis, atopic dermatitis and rheumatoid arthritis, but its wide use is limited by its poor bioavaliability and toxicity, the most significant of which is nephrotoxicity. There has been a tremendous research effort in producing cyclosporin analogues with better pharmacological profiles. This paper will give a general overview of the recent advances (1999 – 2002) made in producing novel semisynthetic cyclosporin analogues with improved bioavailability and therapeutic index.

• calcineurin
• cyclophilin A (CyP)
• cyclosporin A (CsA)
• cyclosporin A analogues
• immunosuppression
• nuclear factor of activated T cells (NFAT)