Discovery of O-Alkylamino-Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents
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- 作者：Haijun Chen ; Zhengduo Yang ; Chunyong Ding ; Lili Chu ; Yusong Zhang ; Kristin Terry ; Huiling Liu ; Qiang Shen ; Jia Zhou
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：February 14, 2013
- 年：2013
- 卷：4
- 期：2
- 页码：180-185
- 全文大小：370K
- 年卷期：v.4,no.2(February 14, 2013)
- ISSN：1948-5875
文摘
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.