MLN4924 (905579-51-3) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor.1 It disrupts cullin-RING ligase-mediated protein turnover leading to apoptosis in human tumor cells. Suppresses the growth of human tumor xenografts in mice.2 Upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma.3 Modulates tumor microenvironment.4 Cell permeable.
1) Soucy, et al. (2009), An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458 732
2) Milhollen, et al. (2010) MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-(kappa)B-dependent lymphoma. Blood, 116 1515
3) Zhou et al. (2019) Neddylation inhibition upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma; Int. J. Cancer, 145 763
4) Zhou et al. (2019) Neddylation: a novel modulator of the tumor microenvironment; Mol. Cancer 18 77