Ohkura Kazuto, Kawaguchi Yuki, Tatematsu Yohei, Uto Yoshihiro, Hori Hitoshi
Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science Graduate School, Suzuka, Japan
Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan.
Anticancer Res. 2016 Jul;36(7):3645-9.
Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K).
Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX-1123 derivatives were examined.
TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 μM), and fit into the pocket of the Src-K molecule as well as c-AMP did.
The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule.
蛋白酪氨酸激酶（PTKs）在细胞增殖和凋亡过程中的信号转导中起主要作用。先前已证明 tyrphostin AG17 是一种有效的肿瘤生长抑制剂，而 AG17 可诱导细胞凋亡并抑制细胞周期蛋白依赖性激酶 2 的活性。我们在此描述 tyrphostin AG17 类似物（如 TX - 1123）与 Src 激酶（Src - K）的结合特征。
从蛋白质数据库（ID = 2SRC）获得 Src - K 的结构数据，并研究 Src - K 与 TX - 1123 衍生物之间的分子相互作用。
TX - 1123 表现出强大的 Src - K 抑制活性（半数最大抑制浓度 = 2.2 μM），并且与 c - AMP 一样能很好地契合 Src - K 分子的口袋。
TX - 1123 衍生物的结合模式彼此不同，而它们的 Src - K 抑制活性受其在 Src - K 分子中的契合情况影响。
