MLN4924

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]. Blocks the neddylation of the DNA endonuclease CtIP, which promotes HDR in Cas9- and Cpf1-mediated gene editing. Part of the CRISPY mix for increasing precise gene editing [5]. Cell permeable.

References:

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