MLN-4924

MLN4924 acts as a Nedd8-activating enzyme inhibitor, blocking proteasomal cullin protein neddylation by Cullin-RING E3 ubiquitin ligases. As a result, these proteins accumulate, inducing cell cycle arrest, senescence, autophagy, and/or apoptosis in cellular and animal models. This compound's inhibition of neddylation decreases NF-kappaB-mediated release of pro-inflammatory cytokines TNF- and IL-6. Pro-angiogenic HIF-1 also accumulates, potentially responsible for downstream inhibition of mTOR and the induction of autophagy.