Cyclosporine analogues

Abstract

Numerous analogues of cyclosporine A (CsA) have been produced and studied. Although these analogues have given considerable insight into structure-activity relationships, none have been shown to have the safety and efficacy of CsA. The most promising of these analogues is cyclosporine G (CsG) in which norvaline is substituted for alpha-aminobutyric acid at the 2 position. Comparative studies of CsG and CsA in animals have produced conflicting results both in terms of nephrotoxicity and the effectiveness of CsG as an immunosuppressive agent. It is evident from these studies that there exist species and strain differences in the metabolism of CsG, sensitivity to its toxic effects and, probably, to its immunological effectiveness. Studies will have to be performed in humans to determine whether, for a given immunosuppressive effect, CsG is less or more toxic than CsA.