NEDD8-activating Enzyme

NEDD8-activating Enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways.

NEDD8 (neural precursor cell expressed developmentally downregulated protein 8) is the ubiquitin-like protein most homologous to ubiquitin. The covalent binding of NEDD8 to substrate proteins is called “neddylation”, and includes the following steps: mature NEDD8 is activated by NEDD8-activating enzyme E1 (NAE), transferred by NEDD8-conjugating enzyme E2, and conjugated to the substrate protein by a NEDD8-E3 ligase.

NAE is a critical regulator of the neddylation pathway. Inhibition of NAE can inhibit the activity of the cullin-RING ligases (CRLs) and result in accumulation of CRL substrate proteins.

Targets for NEDD8-activating Enzyme

Products for NEDD8-activating Enzyme

Cat.No. Product Name Information
GC15086 MLN4924
MLN4924 is a potent and selective small-molecule inhibitor of NEDD8-activating enzyme (NAE) (IC50 = 4 nM), and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50 = 1.5, 8.2, 1.8 and >10 µM, respectively).
GC12175 MLN4924 HCl salt A selective inhibitor of NEDD8-activating enzyme
GC64989 NAcM-OPT NAcM-OPT is an orally bioavailable cullin neddylation 1 (DCN1) inhibitor, which potently inhibits the DCN1-UBE2M interaction.
GC37742 TAS4464
TAS4464 is a highly potent and selective inhibitor of NEDD8 activating enzyme (NAE), with an IC50 of 0.955 nM.
GC37743 TAS4464 hydrochloride TAS4464 (hydrochloride) is a highly potent and selective inhibitor of NEDD8 activating enzyme (NAE), with an IC50 of 0.955 nM.
GC38156 ZM223 hydrochloride ZM223 hydrochloride is an orally active, potent non-covalent NEDD8 activating enzyme (NAE) inhibitor with excellent anticancer activity.