Proteasome Inhibitors for the Treatment of Relapsed Multiple Myeloma: Design and Discovery of Bortezomib and Carfilzomib

This chapter describes the design and development of proteasome inhibitors, bortezomib and carfilzomib, for the treatment of relapsed multiple myeloma. The chapter outlines the ubiquitin-proteasome system, structure–activity studies, boronate-derived proteasome inhibitors, X-ray crystallographic studies, the mechanism of inhibition of epoxomicin, and development of carfilzomib.