NEDD8 and hematologic disorder: However, in contrast to proteasome inhibitors, E1 enzyme inhibitors should not lead to the formation of aggresomes, which are known to limit the therapeutic efficacy of bortezomib and carfilzomib in both hematological malignancies and solid tumors.10–17,20–24 Specifically, this paper reports the discovery of ABP A3, a dual inhibitor of the ubiquitin- and Nedd8-activating E1 enzymes, which inhibits both Nedd8-dependent and Nedd8-independent ubiquitin conjugation and protein degradation.