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

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.

SUBMITTER: Al-Ali H

PROVIDER: S-EPMC6187400 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Al-Ali Hassan H Debevec Ginamarie G Santos Radleigh G RG Houghten Richard A RA Davis Jennifer C JC Nefzi Adel A Lemmon Vance P VP Bixby John L JL Giulianotti Marc A MA

ACS medicinal chemistry letters 20180924 10

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 <i>in vivo</i>. Here, we report the screening of mixture-based co ...[more]

PMID: 30344917

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