具有苯甲酰胺骨架的新型沉默调节蛋白2（SIRT2）抑制剂的设计、合成及构效关系研究
Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton.
作者信息
Sakai Taki, Matsumoto Yotaro, Ishikawa Minoru, Sugita Kazuyuki, Hashimoto Yuichi, Wakai Nobuhiko, Kitao Akio, Morishita Era, Toyoshima Chikashi, Hayashi Tomoatsu, Akiyama Tetsu
机构信息
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.
出版信息
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）。
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