Extracellular cyclophilins in autoimmune diseases and chronic inflammation

Cell penetration is considered a major precondition for the development of a promising drug candidate. The Fischergroup has designed cell impermeant inhibitors of extracellular cyclophilins, enzymes assisting other proteins in their proper folding. Intracellular cyclophilins remain enzymatically active if the inhibitors are delivered to an organism. A common warhead capable of inhibiting cyclophilins will cause immunosuppression and kidney injury when allowed to bind to the intracellular cyclophilin fraction. A sitespecific extracellular action of the newly developed inhibitors suggests future agents can lead to improved therapies.