Proteasome inhibitors: Dozens of molecules and still counting.

The discovery of the proteasome in the late 80's as the core protease of what will be then called the ubiquitin-proteasome system, rapidly followed by the development of specific inhibitors of this enzyme, opened up a new era in biology in the 90's. Indeed, the first proteasome inhibitors were instrumental for understanding that the proteasome is a key actor in most, if not all, cellular processes. The recognition of the central role of this complex in intracellular proteolysis in turn fuelled an intense quest for novel compounds with both increased selectivity towards the proteasome and better bioavailability that could be used in fundamental research or in the clinic.