isocyclosporin A

Isocyclosporin A is a structural isomer of the immunosuppressant cyclosporin A, formed through a reversible N,O-acyl shift. Developed by Dompe' Farmaceutici, it is primarily investigated as a topical ophthalmic prodrug for the treatment of atopic keratoconjunctivitis (AKC). The 'iso' form of the molecule typically demonstrates improved solubility and stability in specific aqueous ophthalmic vehicles compared to the parent cyclosporin A. Upon application to the ocular surface, isocyclosporin A undergoes a pH-dependent conversion back into cyclosporin A. The active cyclosporin A then binds to the intracellular protein peptidyl-prolyl cis-trans isomerase A (cyclophilin A), forming a complex that inhibits the phosphatase activity of calcineurin (protein phosphatase 2B). This inhibition prevents the translocation of the nuclear factor of activated T-cells (NFAT), thereby suppressing the production of pro-inflammatory cytokines like IL-2 and reducing T-cell-mediated ocular inflammation.

Other names

isocyclosporin Aiso-cyclosporin Aisocyclosporineisocyclosporine A