Discovery of Indoline-Based, Natural-Product-like Compounds as Probes of Focal Adhesion Kinase Signaling Pathways

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DOIResolve DOI: http://doi.org/10.1021/cc8001525
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TypeArticle
Journal titleJournal of Combinatorial Chemistry
Volume11
Issue2
Pages303309; # of pages: 7
Subjectindoline-based; molecule modulators; protein; synthesis; aminoindoline-derived; compounds
AbstractWith the goal of identifying small molecule modulators of protein−protein interactions, we developed a solid-phase synthesis method, which was then successfully utilized in a library generation of 164 aminoindoline-derived, natural-product-like compounds. This library and several other related intermediates synthesized during this project were then subjected to different biological assays in search of small molecule modulators of focal adhesion kinase (FAK)-mediated signaling pathways. This study included (i) an in vitro, full length FAK inhibition assay, (ii) a cell proliferation assay, and (iii) a wound healing assay. In FAK inhibition assay, eight library members (5−12) and three aminoindoline derivatives (13, 14, and 2) were identified as promising candidates. Compounds 13 and 2 inhibited the FAK activity by 25−45% at 10 μM. These two lead compounds also showed activity in a wound healing assay. To our knowledge, these aminoindoline-derived small molecules belong to a new family of FAK inhibitors.
Publication date
LanguageEnglish
AffiliationNRC Steacie Institute for Molecular Sciences; National Institute for Nanotechnology; National Research Council Canada
Peer reviewedYes
NPARC number16457845
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Record identifier691a9b0f-eab7-43ac-b727-12235a463b54
Record created2011-02-14
Record modified2016-05-09
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