Deorphaning the Macromolecular Targets of the Natural Anticancer Compound Doliculide.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Schneider, G; Reker, D; Chen, T; Hauenstein, K; Schneider, P; Altmann, K-H

Published Date

  • September 8, 2016

Published In

Volume / Issue

  • 55 / 40

Start / End Page

  • 12408 - 12411

PubMed ID

  • 27605391

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201605707

Language

  • eng