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

作者：Chen Haijun; Yang Zhengduo; Ding Chunyong; Chu Lili; Zhang Yusong; Terry Kristin; Liu Huiling; Shen Qiang^*; Zhou Jia

来源：ACS Medicinal Chemistry Letters, 2013, 4(2): 180-185.

DOI：10.1021/ml3003082

• niclosamide derivatives
• STAT3
• water solubility
• orally bioavailable

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.

• 出版日期2013-2