MLN4924 (Pevonedistat) #85923

MLN4924 (Pevonedistat) is a potent and selective inhibitor of NEDD8-activating enzyme (NAE) (1). The NAE is part of the NEDD8 conjugation pathway that involves the ubiquitin-like NEDD8 protein and cullin-RING ligases (CRL). The NAE is responsible for the covalent attachment of NEDD8 to cullin proteins, termed neddylation, resulting in a conformational change within the CRL, analogous to ubiquitination. This is a reversible, multi-step process responsible for cell cycle progression and survival pathways in cancer cells (2). The inhibition of NAE by MLN4924 (Pevonedistat) induces apoptosis in human tumor cells and reduces human tumor xenograft growth in mice (IC₅₀ = 4.7 nM) (1-3).