Screening for small molecule inhibitors of embryonic pathways: Sometimes you gotta crack a few eggs

Brian I. Hang, Curtis A. Thorne, David J. Robbins, Stacey S. Huppert, Laura A. Lee, Ethan Lee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Extract prepared from Xenopus eggs represents a cell-free system that has been shown to recapitulate a multitude of cellular processes, including cell cycle regulation, DNA replication/repair, and cytoskeletal dynamics. In addition, this system has been used to successfully reconstitute the Wnt pathway. Xenopus egg extract, which can be biochemically manipulated, offers an ideal medium in which small molecule screening can be performed in near native milieu. Thus, the use of Xenopus egg extract for small molecule screening represents an ideal bridge between targeted and phenotypic screening approaches. This review focuses on the use of this system for small molecules modulators of major signal transduction pathways (Notch, Hedgehog, and Wnt) that are critical for the development of the early Xenopus embryo. We describe the properties of Xenopus egg extract and our own high throughput screen for small molecules that modulate the Wnt pathway using this cell-free system. We propose that Xenopus egg extract could similarly be adapted for screening for modulators of the Notch and Hedgehog pathways.

Original languageEnglish (US)
Pages (from-to)1869-1877
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number6
DOIs
StatePublished - Mar 15 2012

Keywords

  • Egg extract
  • Hedgehog signaling
  • High throughput screening
  • Notch signaling
  • Small molecule
  • Wnt signaling
  • Xenopus

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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