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Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling

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Overwhelming evidence that implicates aberrant activations of the canonical Wnt/β-catenin signaling pathway in oncogenesis and cancer progression has emerged in recent times. Accordingly, disruption of this signaling pathway offers an opportunity for effective cancer therapy. Despite various approaches to target components of the Wnt/β-catenin signaling pathway, safe and efficacious therapeutic agents have yet to be identified. As the search for novel small molecule inhibitors remains pressing and continues, natural products, which are traditionally excellent sources of lead compounds in the drug discovery and development process, are gaining prominence as effective antagonists of the signaling pathway. In this review, we will provide a comprehensive summary on the current use of natural compounds ranging from plant-derived polyphenols, anti-malarial artemisinins to several antimicrobial products as Wnt therapeutics and the development of more efficacious semi-synthetic analogues using these compounds as lead structures. We will also discuss pertinent issues that are limiting the rate of drug development based on these compounds and the chemical-biological significance across the diverse classes of natural compounds. The findings reviewed here should inspire and motivate more efforts to harness rich and diverse plant and other natural sources in the search for new leads as effective antagonists of the Wnt/β-catenin pathway.

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Keywords: Wnt/β-catenin; antagonists; drug development; inhibitors; natural compounds

Document Type: Research Article

Publication date: January 1, 2010

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  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).
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