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Blood, 30 July 2009, Vol. 114, No. 5, pp. 1110-1122. Prepublished online as a Blood First Edition Paper on May 28, 2009; DOI 10.1182/blood-2009-03-211771. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figure All Versions of this Article: blood-2009-03-211771v1 114/5/1110    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kälin, R. E. Articles by Brändli, A. W. Search for Related Content PubMed PubMed Citation Articles by Kälin, R. E. Articles by Brändli, A. W. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis Roland E. Kälin*,1, Nadja E. Bänziger-Tobler*,1, Michael Detmar1, and André W. Brändli1 1 Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland Angiogenesis and lymphangiogenesis are essential for organogenesis but also play important roles in tissue regeneration, chronic inflammation, and tumor progression. Here we applied in vivo forward chemical genetics to identify novel compounds and biologic mechanisms involved in (lymph)angiogenesis in Xenopus tadpoles. A novel 2-step screening strategy involving a simple phenotypic read-out (edema formation or larval lethality) followed by semiautomated in situ hybridization was devised and used to screen an annotated chemical library of 1280 bioactive compounds. We identified 32 active compounds interfering with blood vascular and/or lymphatic development in Xenopus. Selected compounds were also tested for activities in a variety of endothelial in vitro assays. Finally, in a proof-of-principle study, the adenosine A1 receptor antagonist 7-chloro-4-hydroxy-2-phenyl-1,8-naphthyridine, an inhibitor of blood vascular and lymphatic development in Xenopus, was shown to act also as a potent antagonist of VEGFA-induced adult neovascularization in mice. Taken together, the present chemical library screening strategy in Xenopus tadpoles represents a rapid and highly efficient approach to identify novel pathways involved in (lymph)angiogenesis. In addition, the recovered compounds represent a rich resource for in-depth analysis, and their drug-like features will facilitate further evaluation in preclinical models of inflammation and cancer metastasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Oliver and R. S. Srinivasan Endothelial cell plasticity: how to become and remain a lymphatic endothelial cell Development, February 1, 2010; 137(3): 363 - 372. [Abstract] [Full Text] [PDF] F. Bruyere and A. Noel Lymphangiogenesis: in vitro and in vivo models FASEB J, January 1, 2010; 24(1): 8 - 21. [Abstract] [Full Text] [PDF]

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