MLN4924

NEDD8 is an ubiquitin-like protein whose activity is required to activate cullin-RING ubiquitin E3 ligases (CRLs) responsible for the ubiquitination and proteasome-dependent turnover of certain substrates with roles relevant to cellular processes important for cancer cell survival. Neddylation of CRLs is initiated by NEDD8-activating enzyme (NAE), which has become a novel target in cancer therapeutic research. MLN4924 is an analog of adenosine 5'-monophosphate that selectively inhibits NAE (IC50 = 4.7 nM). At much higher concentrations, MLN4924 inhibits the related enzymes ubiquitin-activating enzyme (UAE) and SUMO-activating enzyme (SAE) with IC50 values of 1.5 and 8.2 µM, respectively. At 0.3 µM, MLN4924 has been shown to disrupt CRL-mediated protein turnover leading to apoptosis in HCT116 cells by deregulating S-phase DNA synthesis. In vivo, 30-60 mg/kg MLN4924 dose-dependently suppresses the growth of human tumor xenografts in mice.Formal Name: sulfamic acid, [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester. CAS Number: 905579-51-3. Synonyms: Pevonedistat. Molecular Formula: C21H25N5O4S. Formula Weight: 443.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 12.5 mg/ml. lambdamax: 213, 279 nm. SMILES: O[C@H]([C@H](COS(N)(=O)=O)C1)C[C@@H]1N2C=CC3=C(N[C@@H]4C(C=CC=C5)=C5CC4)N=CN=C23. InChi Code: InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1. InChi Key: MPUQHZXIXSTTDU-QXGSTGNESA-N.