Discovery of O-Alkylamino-Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents

被引：116

作者：

Chen, Haijun ^{[1
]}

Yang, Zhengduo ^{[2
]}

Ding, Chunyong ^{[1
]}

Chu, Lili ^{[2
]}

Zhang, Yusong ^{[2
]}

Terry, Kristin ^{[2
]}

Liu, Huiling ^{[1
]}

Shen, Qiang ^{[2
]}

Zhou, Jia ^{[1
]}

机构：

[1] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Chem Biol Program, Galveston, TX 77555 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 02期

关键词：

niclosamide derivatives; STAT3; water solubility; orally bioavailable; SMALL-MOLECULE INHIBITOR; STAT PROTEINS; CANCER; TARGETS; SOLUBILITY; BREAST; TUMORS;

D O I：

10.1021/ml3003082

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide have hindered its further clinical development for cancer therapy. To discover new molecules with enhanced druglike properties, a series of novel O-alkylamino-tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound 11 (HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growth in vivo (ip and po), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.

引用

页码：180 / 185

页数：6

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