E2012

E2012 is a modulator of gamma-secretase. It selectively inhibits APP intracellular signaling domain (AICD) cleavage to amyloid-beta (Abeta) over Notch cleavage to its signaling effector Notch intracellular domain (NICD), processes both mediated by gamma-secretase, when used at a concentration of 1 µM in luciferase assays. E2012 also inhibits the activity of the cholesterol synthesis enzyme 3beta-hydroxysterol ?24-reductase (DHCR24) in primary rat hepatocytes and HepG2 cells (IC50s = 11 and 15 nM, respectively). It reduces Abeta (1-42) (Abeta42) production in primary rat embryonic cerebral cortex neurons with an IC50 value of 220 nM. E2012 (100 mg/kg) also decreases Abeta42 levels in guinea pig brain and cerebral spinal fluid (CSF).Formal Name: (3E)-1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylene]-2-piperidinone. CAS Number: 870843-42-8. Molecular Formula: C25H26FN3O2. Formula Weight: 419.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 10mg/mL, DMSO: 10mg/mL, DMSO:PBS (pH 7.2) (1:3): 0.25mg/mL, Ethanol: 10mg/mL. lambdamax: 286 nm. SMILES: FC1=CC=C([C@H](C)N2C(/C(CCC2)=C/C3=CC(OC)=C(N4C=NC(C)=C4)C=C3)=O)C=C1. InChi Code: InChI=1S/C25H26FN3O2/c1-17-15-28(16-27-17)23-11-6-19(14-24(23)31-3)13-21-5-4-12-29(25(21)30)18(2)20-7-9-22(26)10-8-20/h6-11,13-16,18H,4-5,12H2,1-3H3/b21-13+/t18-/m0/s1. InChi Key: PUOAETJYKQITMO-LANLRWRYSA-N.