High-content analysis of proapoptotic EphA4 dependence receptor functions using small-molecule libraries

Claudiu M. Nelersa, Henry Barreras, Erik Runko, Jerome Ricard, Yan Shi, Stephanie J. Glass, John L. Bixby, Vance P. Lemmon, Daniel J. Liebl

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Small-molecule compounds (SMCs) can provide an inexpensive and selective approach to modifying biological responses. High-content analysis (HCA) of SMC libraries can help identify candidate molecules that inhibit or activate cellular responses. In particular, regulation of cell death has important implications for many pathological conditions. Dependence receptors are a new classification of proapoptotic membrane receptors that, unlike classic death receptors, initiate apoptotic signals in the absence of their ligands. EphA4 has recently been identified as a dependence receptor that may have important functions in conditions as disparate as cancer biology and CNS injury and disease. To screen potential candidate SMCs that inhibit or activate EphA4-induced cell death, HCA of an SMC library was performed using stable EphA4-expressing NIH 3T3 cells. Our results describe a high-content method for screening dependence receptor-signaling pathways and demonstrate that several candidate SMCs can inhibit EphA4-mediated cell death.

Original languageEnglish (US)
Pages (from-to)785-795
Number of pages11
JournalJournal of Biomolecular Screening
Issue number6
StatePublished - Jul 2012


  • apoptosis
  • dependence receptor
  • Eph receptors
  • ephrins
  • high-content screen

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology


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