Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents

Haijun Chen, Zhengduo Yang, Chunyong Ding, Lili Chu, Yusong Zhang, Kristin Terry, Huiling Liu, Qiang Shen, Jia Zhou

Research output: Contribution to journalArticle

66 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)180-185
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume4
Issue number2
DOIs
StatePublished - Feb 14 2013

    Fingerprint

Keywords

  • STAT3
  • niclosamide derivatives
  • orally bioavailable
  • water solubility

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this