1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2

Lorna M. Cryan, Lauren Bazinet, Kaiane A. Habeshian, Shugeng Cao, Jon Clardy, Kenneth A. Christensen, Michael S. Rogers

Research output: Contribution to journalArticle

Abstract

Capillary morphogenesis gene 2 (CMG2) is a transmembrane extracellular matrix binding protein that is also an anthrax toxin receptor. We have shown that high-affinity CMG2 binders can inhibit angiogenesis and tumor growth. We recently described a high-throughput FRET assay to identify CMG2 inhibitors. We now report the serendipitous discovery that PGG (1,2,3,4,6-penta-O-galloyl- β-d-glucopyranose) is a CMG2 inhibitor with antiangiogenic activity. PGG is a gallotannin produced by a variety of medicinal plants that exhibits a wide variety of antitumor and other activities. We find that PGG inhibits CMG2 with a submicromolar IC50 and it also inhibits the migration of human dermal microvascular endothelial cells at similar concentrations in vitro. Finally, oral or intraperitoneal administration of PGG inhibits angiogenesis in the mouse corneal micropocket assay in vivo. Together, these results suggest that a portion of the in vivo antitumor activity of PGG may be the result of antiangiogenic activity mediated by inhibition of CMG2.

Original languageEnglish (US)
Pages (from-to)1940-1945
Number of pages6
JournalJournal of medicinal chemistry
Volume56
Issue number5
DOIs
StatePublished - Mar 14 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Cryan, L. M., Bazinet, L., Habeshian, K. A., Cao, S., Clardy, J., Christensen, K. A., & Rogers, M. S. (2013). 1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2. Journal of medicinal chemistry, 56(5), 1940-1945. https://doi.org/10.1021/jm301558t