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

Authors

Hassan Al-Ali, University of Miami
Ginamarie Debevec, Torrey Pines Institute for Molecular Studies
Radleigh Santos, Torrey Pines Institute for Molecular StudiesFollow
Richard A. Houghten, Torrey Pines Institute for Molecular Studies
Jennifer C. Davis, Torrey Pines Institute for Molecular Studies
Adel Nefzi, Torrey Pines Institute for Molecular Studies
Vance P. Lemmon, University of Miami
John L. Bixby, University of Miami
Marc A. Giulianotti, Torrey Pines Institute for Molecular Studies

Document Type

Article

Publication Date

9-24-2018

Publication Title

ACS Medicinal Chemistry Letters

Keywords

Nerve repair, Axon regeneration, Neurite outgrowth, Phenotypic screening

ISSN

1948-5875

Volume

9

Issue/No.

10

First Page

1057

Last Page

1062

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.

Comments

©2018 American Chemical Society

NSUWorks Citation

Al-Ali, Hassan; Debevec, Ginamarie; Santos, Radleigh; Houghten, Richard A.; Davis, Jennifer C.; Nefzi, Adel; Lemmon, Vance P.; Bixby, John L.; and Giulianotti, Marc A., "Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency" (2018). Mathematics Faculty Articles. 285.
https://nsuworks.nova.edu/math_facarticles/285

DOI

10.1021/acsmedchemlett.8b00425