Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency

Hassan Al-Ali, Ginamarie Debevec, Radleigh G. Santos, Richard A. Houghten, Jennifer C. Davis, Adel Nefzi, Vance P. Lemmon, John L. Bixby, Marc A. Giulianotti

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Central nervous system (CNS) neurons typically fail to regrow their axons after injury. Injuries or neuropathies that damage CNS axons and disrupt neuronal circuitry often result in permanent functional deficits. Axon regeneration is therefore an intensely pursued therapeutic strategy for numerous CNS disorders. Phenotypic screens utilizing primary neurons have proven successful at identifying agents that promote axon regeneration in vivo. Here, we report the screening of mixture-based combinatorial small molecule libraries in a phenotypic assay utilizing primary CNS neurons and the discovery of neurite outgrowth promoters with low nanomolar potency.

Original languageEnglish (US)
Pages (from-to)1057-1062
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume9
Issue number10
DOIs
StatePublished - Oct 11 2018

Keywords

  • Nerve repair
  • axon regeneration
  • neurite outgrowth
  • phenotypic screening

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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