The first naturally occurring Tie2 kinase inhibitor.
[structure: see text] Bioassay-guided fractionation of the plant Acacia aulacocarpa, guided by a bioassay for Tie2 tyrosine kinase activity, yielded the novel triterpene 3,21-dioxo-olean-18-en-oic acid (1) as the first naturally occurring non-protein inhibitor of Tie2 kinase. The structure of 1 was assigned by analysis of spectral data. In addition to its activity as an inhibitor of Tie2 kinase, compound 1 also shows modest activity against a variety of cultured mammalian cells.
Zhou
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Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Johnson
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RK
Mattern
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MR
Fisher
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Kingston
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DG
D000045:Acacia / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042787:Receptor, TIE-2; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
C447982:3,21-dioxo-olean-18-en-oic acid; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D014315:Triterpenes; D009828:Oleanolic Acid; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2