Discovery of a small molecular compound simultaneously targeting RXR and HADC: Design, synthesis, molecular docking and bioassay

被引：16

作者：

Chen, Guo-Liang ^{[1
]}

Wang, Li-Hui ^{[2
,3
]}

Wang, Jian ^{[1
]}

Chen, Kang ^{[2
,3
]}

Zhao, Man ^{[1
]}

Sun, Zhao-Zhu ^{[1
]}

Wang, Shuang ^{[2
,3
]}

Zheng, Hong-Li ^{[2
,3
]}

Yang, Jing-Yu ^{[2
,3
]}

Wu, Chun-Fu ^{[2
,3
]}

机构：

[1] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drugs Design & Discovery, Shenyang 110016, Peoples R China

[2] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China

[3] Shenyang Pharmaceut Univ, Benxi Inst Pharmaceut Res, Shenyang 110016, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 13期

基金：

国家高技术研究发展计划(863计划); 中国博士后科学基金;

关键词：

Retinoid X receptors; Histone deacetylase; Dual-target; Anti-cancer; HISTONE DEACETYLASE INHIBITORS; CANCER; BEXAROTENE; VORINOSTAT; ACID;

D O I：

10.1016/j.bmcl.2013.04.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-targeting agent is derived from bexarotene and suberoylanilide hydroxamic acid (SAHA), prototypical RXR agonist and HDAC inhibitor, respectively. Molecular docking studies demonstrate that this agent has a relatively strong affinity to RXR and HADC. Importantly, it presents the potentials of activation of RXR and inhibition of HDAC in both cell-free and whole-cell assays, and displays anti-proliferative effect on representative cancer cell lines and drug-resistant cancer cell lines. (c) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3891 / 3895

页数：5

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