Fluorinated N, N -dialkylaminostilbenes for wnt pathway inhibition and colon cancer repression

Wen Zhang, Vitaliy Sviripa, Liliia M. Kril, Xi Chen, Tianxin Yu, Jiandang Shi, Piotr Rychahou, B. Mark Evers, David S. Watt, Chunming Liu

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the USA. CRC is initiated by mutations of the tumor suppressor gene, adenomatous polyposis coli (APC), or β-catenin gene. These mutations stabilize β-catenin and constitutively activate Wnt/β-catenin target genes, such as c-Myc and cyclin D1, ultimately leading to cancer. Naturally occurring stilbene derivatives, resveratrol and pterostilbene, inhibit Wnt signaling and repress CRC cell proliferation but are ineffective at concentrations less than 10 μM. To understand the structure-activity relationship within these stilbene derivatives and to develop more efficacious Wnt inhibitors than these natural products, we synthesized and evaluated a panel of fluorinated N,N-dialkylaminostilbenes. Among this panel, (E)-4-(2,6-difluorostyryl)-N,N-dimethylaniline (4r) inhibits Wnt signaling at nanomolar levels and inhibits the growth of human CRC cell xenografts in athymic nude mice at a dosage of 20 mg/kg. These fluorinated N,N-dialkylaminostilbenes appear to inhibit Wnt signaling downstream of β-catenin, probably at the transcriptional level.

Original languageEnglish
Pages (from-to)1288-1297
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number5
StatePublished - Mar 10 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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