title: Discovery ofO-Alkylamino Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents.
abstract: Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide has hindered its further clinical development for cancer therapy. To discover new molecules with enhanced drug-like properties, a series of novelO-alkylamino tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound11(HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growthin vivo(i.p. & p.o.), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.
authors: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, United States.
authors: Haijun
authors: H
authors: Chen
authors: Zhengduo
authors: Z
authors: Yang
authors: Chunyong
authors: C
authors: Ding
authors: Lili
authors: L
authors: Chu
authors: Yusong
authors: Y
authors: Zhang
authors: Kristin
authors: K
authors: Terry
authors: Huiling
authors: H
authors: Liu
authors: Qiang
authors: Q
authors: Shen
authors: Jia
authors: J
authors: Zhou
keywords: Niclosamide derivatives; STAT3; orally bioavailable; water solubility