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

  • ACS Med Chem Lett. 2013 Feb 14;4(2):180-185. doi: 10.1021/ml3003082.
Haijun Chen  1 ,  Zhengduo Yang ,  Chunyong Ding ,  Lili Chu ,  Yusong Zhang ,  Kristin Terry ,  Huiling Liu ,  Qiang Shen ,  Jia Zhou
Affiliations
  • 1. Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, United States.
PMID: 23459613 DOI: 10.1021/ml3003082
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 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 (i.p. & p.o.), indicating its great potential as efficacious and orally bioavailable therapeutics for human Cancer.

Keywords
Niclosamide derivatives; STAT3; orally bioavailable; water solubility.
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