The First Naturally Occurring Tie2
Kinase Inhibitor
Bing-Nan Zhou,Randall K. Johnson,Michael R. Mattern,Paul W. Fisher, and
David G. I. Kingston*
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State
University, Blacksburg, Virginia 24061, and GlaxoSmithKline Pharmaceuticals,
709 Swedeland Road, King of Prussia, Pennsylvania 19406-0939
dkingston@vt.edu
Received September 18, 2001
Abstract:
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.
