Deorphaning the Macromolecular Targets of the Natural Anticancer Compound Doliculide. (8th September 2016)

• Record Type: Journal Article
• Authors: Schneider, Gisbert; Reker, Daniel; Chen, Tao; Hauenstein, Kurt; Schneider, Petra; Altmann, Karl‐Heinz
• Is Part Of: Angewandte Chemie. Volume 128:Number 40(2016)
• Page Start: 12596
• Page End: 12599
• Publication Date: 2016-09-08
• Subjects: Chemoinformatik -- Naturstoffe -- Polypharmakologie -- Tumortherapeutika -- Wirkstoff-Forschung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201605707
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The cyclodepsipeptide doliculide is a marine natural product with strong actin‐polymerizing and anticancer activities. Evidence for doliculide acting as a potent and subtype‐selective antagonist of prostanoid E receptor 3 (EP3) is presented. Computational target prediction suggested that this membrane receptor is a likely macromolecular target and enabled immediate in vitro validation. This proof‐of‐concept study demonstrates the in silico deorphanization of phenotypic screening hits as a viable concept for future natural‐product‐inspired chemical biology and drug discovery efforts.