Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 16, Issue 21, Pages 9596-9602Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.09.025
Keywords
Natural products; Natural product-like compounds; Small-molecule chemical probes; Diversity-oriented synthesis; Focal adhesion kinase; Signaling networks; Cell migration; Anti-cancer agents; Docking
Funding
- NRC Genomics and Health Initiative
- Canadian Cancer Society (CCS)
- National Cancer Institute of Canada (NCIC)
- Canadian Institutes of Health Research (CIHR)
- Government of Ontario
- Canadian Foundation for Innovation
- Ontario Genomics Institute
- GlaxoSmithKline
- Karolinska Institutet
- Knut and Alice Wallenberg Foundation
- Ontario Innovation Trust
- Ontario Ministry for Research and Innovation
- Merck
- Novartis Research Foundation
- Swedish Agency for Innovation Systems
- Swedish Foundation for Strategic Research
- Wellcome Trust
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Inspired by bioactive indoline alkaloid natural products, here, we report a divergent synthesis approach that led to skeletally diverse indoline alkaloid-inspired compounds. The natural product-inspired compounds obtained were then subjected to a series of in vitro and cellular assays to examine their properties as modulators of focal adhesion kinase (FAK) activity. This study resulted in the identification of a promising lead inhibitor of FAK (42), which also showed activity in a wound healing and cell invasion assay. The in silico study of the lead compound (42) was also undertaken. (C) 2008 Elsevier Ltd. All rights reserved.
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