NB-598: a potent competitive inhibitor of squalene epoxidase.
NB-598: a potent competitive inhibitor of squalene epoxidase.
复制标题
DOI：
10.1016/s0021-9258(17)44716-8
复制
发表时间：
1990-10
期刊：
影响因子：
--
通讯作者：
M. Horie;Y. Tsuchiya;M. Hayashi;Y. Iida;Y. Iwasawa;Y. Nagata;Y. Sawasaki;H. Fukuzumi;K. Kitani;T. Kamei
中科院分区：
文献类型：
--
作者：
M. Horie;Y. Tsuchiya;M. Hayashi;Y. Iida;Y. Iwasawa;Y. Nagata;Y. Sawasaki;H. Fukuzumi;K. Kitani;T. Kamei
NB-598，(E)N-乙基-N-(6,6-二甲基-2-庚烯-4-炔基)-3-[(3,3'-二碘苯-5-基)甲氧基]苯-甲胺，被发现以竞争性方式抑制人微粒体角鲨烯环氧化酶（来自 Hep G2 细胞）。 NB-598 在 Hep G2 细胞中剂量依赖性地抑制 [14C]乙酸酯合成胆固醇，并增加角鲨烯的细胞内放射性。单次口服 NB-598 可抑制大鼠体内 [14C]乙酸的胆固醇合成。此外，对狗多次口服NB-598可降低血清总胆固醇和低密度脂蛋白胆固醇水平，并增加血清角鲨烯水平。治疗结束后，降低的血清胆固醇和升高的角鲨烯水平恢复到对照值。
NB-598, (E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bith iophen-5-yl)methoxy]benzene-methanamine, was found to inhibit human microsomal squalene epoxidase (from Hep G2 cells) in a competitive manner. NB-598 inhibited cholesterol synthesis from [14C]acetate dose dependently in Hep G2 cells and increased the intracellular radioactivity of squalene. A single oral administration of NB-598 inhibited cholesterol synthesis from [14C]acetate in rats. Moreover, multiple oral administration of NB-598 to dogs decreased serum total and low density lipoprotein cholesterol levels and increased serum squalene levels. After termination of treatment, the reduced serum cholesterol and increased squalene levels returned to their control values.