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Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

doi: 10.1016/j.eururo.2018.09.030 42 OhMHSunIHZhaoLLeoneRDSunIMXuWet al

Similar rescuing effects of acetate on protein and RNA level were observed upon silencing of ULK1 (Supplementary Figure Fig

wherein the ligand is selected from the group consisting of: glutathione, S-(p-bromobenzyl)glutathione, gamma-(L-gamma-azaglutamyl)-S-(p-bromobenzyl)-L-cysteinylglycin, S-butylglutathione, S-decylglutathione, glutathione reduced ethyl ester, glutathionesulfonic acid, S-hexylglutathione, S-lactoylglutathione, S-methylglutathione, S-(4-nitrobenzyl)glutathione, S-octylglutathione, S-propylglutathione, n-butanoyl gamma-glutamylcysteinylglycine, ethanoyl gamma-glutamylcysteinylglycine, hexanoyl gamma-glutamylcysteinylglycine, octanoyl gamma-glutamylcysteinylglycine, dodecanoyl gamma-glutamylcysteinylglycine, GSH monoisopropyl ester (N-(N-L-glutamyl-L-cysteinyl)glycine 1-isopropyl ester sulfate monohydrate) and glutathione derivatives of the formula I:wherein Z=CH 2 and Y=CH 2 , or Z=O and Y = C=O;R 1 and R 2 are independently selected from the group consisting of:i) H,ii) linear or branched alkyl (1-25C),iii) aralkyl (6-26C),iv) cycloalkyl (6-25C),v) heterocycles (6-20C),vi) ethers or polyethers (3-25C), andvii) where R 1 -R 2 together have 2-20C atoms and form a macrocycle with the remainder of formula I;R 3 is selected from the group consisting of H and CH 3 ;R4 is selected form the group consisting of 6-8C alkyl, benzyl, naphthyl and a therapeutically active compound