Deorphaning the Macromolecular Targets of the Natural Anticancer Compound Doliculide.

TitleDeorphaning the Macromolecular Targets of the Natural Anticancer Compound Doliculide.
Publication TypeJournal Article
Year of Publication2016
AuthorsG Schneider, D Reker, T Chen, K Hauenstein, P Schneider, and K-H Altmann
JournalAngewandte Chemie International Edition
Volume55
Start Page12408
Issue40
Pagination12408 - 12411
Date Published09/2016
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.

DOI10.1002/anie.201605707
Short TitleAngewandte Chemie International Edition