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 journalArticle

6 Citations (Scopus)

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

Fingerprint

Xenopus
Eggs
Screening
Cracks
Molecules
Ovum
Modulators
Wnt Signaling Pathway
Hedgehogs
Cell-Free System
Signal transduction
Repair
Cells
Throughput
DNA Replication
DNA Repair
Signal Transduction
DNA
Cell Cycle
Embryonic Structures

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

Cite this

Screening for small molecule inhibitors of embryonic pathways : Sometimes you gotta crack a few eggs. / Hang, Brian I.; Thorne, Curtis A.; Robbins, David J; Huppert, Stacey S.; Lee, Laura A.; Lee, Ethan.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 6, 15.03.2012, p. 1869-1877.

Research output: Contribution to journalArticle

Hang, Brian I. ; Thorne, Curtis A. ; Robbins, David J ; Huppert, Stacey S. ; Lee, Laura A. ; Lee, Ethan. / Screening for small molecule inhibitors of embryonic pathways : Sometimes you gotta crack a few eggs. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 6. pp. 1869-1877.
@article{26da22aa65bd422aac39609567df2917,
title = "Screening for small molecule inhibitors of embryonic pathways: Sometimes you gotta crack a few eggs",
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.",
keywords = "Egg extract, Hedgehog signaling, High throughput screening, Notch signaling, Small molecule, Wnt signaling, Xenopus",
author = "Hang, {Brian I.} and Thorne, {Curtis A.} and Robbins, {David J} and Huppert, {Stacey S.} and Lee, {Laura A.} and Ethan Lee",
year = "2012",
month = "3",
day = "15",
doi = "10.1016/j.bmc.2011.12.044",
language = "English",
volume = "20",
pages = "1869--1877",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "6",

}

TY - JOUR

T1 - Screening for small molecule inhibitors of embryonic pathways

T2 - Sometimes you gotta crack a few eggs

AU - Hang, Brian I.

AU - Thorne, Curtis A.

AU - Robbins, David J

AU - Huppert, Stacey S.

AU - Lee, Laura A.

AU - Lee, Ethan

PY - 2012/3/15

Y1 - 2012/3/15

N2 - 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.

AB - 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.

KW - Egg extract

KW - Hedgehog signaling

KW - High throughput screening

KW - Notch signaling

KW - Small molecule

KW - Wnt signaling

KW - Xenopus

UR - http://www.scopus.com/inward/record.url?scp=84857910505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857910505&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2011.12.044

DO - 10.1016/j.bmc.2011.12.044

M3 - Article

C2 - 22261025

AN - SCOPUS:84857910505

VL - 20

SP - 1869

EP - 1877

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 6

ER -