Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Halbedl, Sonja, Kratzer, Marie-Claire, Rahm, Karolin, Crosta, Nicoletta, Masters, Kye-Simeon, Zippert, Jessica, Bräse, Stefan, & Gradl, Dietmar (2013) Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin. FEBS Letters, 587(5), pp. 522-527.

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Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

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3 citations in Scopus
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5 citations in Web of Science®

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ID Code: 69694
Item Type: Journal Article
Refereed: Yes
DOI: 10.1016/j.febslet.2013.01.034
ISSN: 0014-5793
Subjects: Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > MEDICINAL AND BIOMOLECULAR CHEMISTRY (030400)
Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > ORGANIC CHEMISTRY (030500) > Organic Chemical Synthesis (030503)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2013 Federation of European Biochemical Societies
Copyright Statement: This is the author’s version of a work that was accepted for publication in FEBS Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in FEBS Letters, [VOL 587, ISSUE 5, (2013)] DOI: 10.1016/j.febslet.2013.01.034
Deposited On: 03 Apr 2014 01:10
Last Modified: 03 Apr 2014 22:31

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