Sakai Taki, Matsumoto Yotaro, Ishikawa Minoru, Sugita Kazuyuki, Hashimoto Yuichi, Wakai Nobuhiko, Kitao Akio, Morishita Era, Toyoshima Chikashi, Hayashi Tomoatsu, Akiyama Tetsu
Laboratory of Bioorganic Chemistry, Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Laboratory of Bioorganic Chemistry, Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Bioorg Med Chem. 2015 Jan 15;23(2):328-39. doi: 10.1016/j.bmc.2014.11.027. Epub 2014 Dec 2.
Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synthesized a series of benzamide derivatives as SIRT2 inhibitor candidates. Among them, compound 17k showed the most potent SIRT2-inhibitory activity (IC50=0.60μM), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 >100μM).
人类沉默调节蛋白2（SIRT2）是开发治疗神经退行性疾病和癌症药物的一个有吸引力的靶标分子，因为SIRT2抑制剂对神经退行性变具有保护作用，并且对癌症干细胞具有抗增殖作用。我们设计并合成了一系列苯甲酰胺衍生物作为SIRT2抑制剂候选物。其中，化合物17k表现出最有效的SIRT2抑制活性（IC50 = 0.60μM），对SIRT1和SIRT3亚型的选择性超过150倍（IC50> 100μM）。
