MLN4924 inhibits cullin neddylation by directly targeting the NEDD8-activating enzyme that is essential for the activity of cullin-RING ligase (CRL) (Nawrocki et al.) The components of CRL are frequently up-regulated in human cancers (Zhao & Sun), and MLN4924 was reported to suppress the growth of human tumor xenografts in mice (Soucy et al.)
In combination with other small molecules ('CRISPY' mix), MLN4924 has been reported to increase precise CRISPR-Cas9 genome editing in human pluripotent stem cells (Riesenberg & Maricic)
By blocking NAE and proteasome, MLN4924 together with bortezomib inhibits AKT and mTOR and induces apoptosis in multiple myeloma cell lines (Gu et al.)
