title: Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine.
abstract: To identify cell-active sirtuin inhibitors containing N-thioacetyl lysine, we synthesized compound 1, which was designed based on the structure of the reported N-ethoxycarbonylacetyl lysine-based sirtuin inhibitor NCS-12k. Compound 1 selectively inhibited SIRT1 in enzyme assays. Compound 1 also caused a dose-dependent increase in p53 acetylation in human colon cancer HCT116 cells, indicating the inhibition of SIRT1 in these cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Asaba
authors.forename: Erika
authors.initials: E
authors.lastname: Imai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsumoto
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
mesh_terms: D000107:Acetylation; D045325:HCT116 Cells; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D013854:Thioamides; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D037761:Sirtuins; D008239:Lysine