一种作为蛋白酪氨酸激酶抑制剂的抗肿瘤2-羟基亚芳基-4-环戊烯-1,3-二酮：TX-1123衍生物与Src激酶之间的相互作用

An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1,3-Dione as a Protein Tyrosine Kinase Inhibitor: Interaction Between TX-1123 Derivatives and Src Kinase.

作者信息

Ohkura Kazuto, Kawaguchi Yuki, Tatematsu Yohei, Uto Yoshihiro, Hori Hitoshi

机构信息

Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science Graduate School, Suzuka, Japan

Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan.

出版信息

Anticancer Res. 2016 Jul;36(7):3645-9.

PMID:27354635

Abstract

BACKGROUND

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).

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。