Biochemicals & reagents
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
MLN4924 is a potent and selective NEDD8-activating enzyme (NAE) inhibitor (1) which disrupts cullin-RING ligase-mediated protein turnover leading to apoptosis in human tumor cells and suppresses the growth of human tumor xenografts in mice (2). This compound upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma (3). It also modulates tumor microenvironment (4) and is cell permeable.