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Structural information on the yCP alone and in complex with ligands strongly supported the development of the currently known potent CP inhibitors bortezomib and carfilzomib. Both compounds do not discriminate between the three mammalian CP types and, thereby, exert anti-cancer activity. However, recent studies demonstrate that iCP-specific inhibitors might qualify as therapeutics in autoimmune diseases. So far, only a few iCP-specific inhibitors were identified, mostly because structural data on the iCP were lacking.