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

作者: Wen Zhang , Vitaliy Sviripa , Liliia M. Kril , Xi Chen , Tianxin Yu

DOI: 10.1021/JM101248V

关键词:

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

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