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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.

Cat. No. Product Name CAS No. Information
GY02187

MLN-4924 hydrochloride

1160295-21-5

An analog of adenosine 5’-monophosphate that potently and selectively inhibits NEDD8-activating enzyme (NAE) with IC50 of 4.7 nM; also inhibits the related enzymes ubiquitin-activating enzyme (UAE) and SUMO-activating enzyme (SAE) with IC50 of 1.5 and 8.2 uM, respectively; disrupts CRL-mediated protein turnover leading to apoptosis in HCT116 cells, suppresses the growth of human tumor xenografts in mice (30-60 mg/kg).

GY01361

Pevonedistat

905579-51-3

Pevonedistat ia an analog of adenosine 5’-monophosphate that potently and selectively inhibits NEDD8-activating enzyme (NAE) with IC50 of 4.7 nM; also inhibits the related enzymes ubiquitin-activating enzyme (UAE) and SUMO-activating enzyme (SAE) with IC50 of 1.5 and 8.2 uM, respectively; disrupts CRL-mediated protein turnover leading to apoptosis in HCT116 cells, suppresses the growth of human tumor xenografts in mice (30-60 mg/kg).

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