molecules of the month

ASP5286 is an analog of the natural product cyclosporin A that maintains the anti-HCV activity of cyclosporin A by binding to cyclophilin, but was optimized to be less immunosuppresive than cyclosporin A. The macrocycle was identified through semisynthetic derivitization of a related natural product, FR901459. The Astellas team was able to optimize compounds from immunosuppresive compounds with poor oral exposure to the non-immunosuppressive clinical candidate 5286 with oral activity in a mouse humanized liver HCV model.