alexa J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeTox™ Safety and Genotoxicity Analysis | OMICS International | Abstract
ISSN: 2155-9562

Journal of Neurology & Neurophysiology
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Research Article

J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeTox™ Safety and Genotoxicity Analysis

Paul A Lapchak1*, Rene Bombien2 and Padmesh S Rajput3

1Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA

2Division of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, USA

3Department of Neurology, Advanced Health Sciences Pavilion, Los Angeles, USA

Corresponding Author:
Paul A Lapchak, PhD, FAHA
Department of Neurology & Neurosurgery
Cedars-Sinai Medical Center
Advanced Health Sciences Pavilion, USA
Tel: 310-248-8188
Fax: 310-248-7568
E-mail: [email protected]

Received date: June 21, 2013; Accepted date: July 18, 2013; Published date: July 25, 2013

Citation: Lapchak PA, Bombien R, Rajput PS (2013) J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeTox™ Safety and Genotoxicity Analysis. J Neurol Neurophysiol 4:158. doi:10.4172/2155-9562.1000158

Copyright: © 2013 Lapchak PA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

J-147 is a broad spectrum neuroprotective phenyl hydrazide compound with significant neurotrophic properties related to the induction of brain-derived neurotrophic factor (BDNF). Because this molecule is pleiotropic, it may have substantial utility in the treatment of a wide range of neurodegenerative diseases including acute ischemic stroke (AIS), traumatic brain injury(TBI), and Alzheimer’s disease(AD) where both neuroprotection and neurotrophism would be beneficial. Because of the pleiotropic actions of J-147, we sought to determine the safety profile of the drug using multiple assay analysis. For CeeTox analyses, we used a rat hepatoma cell line (H4IIE) resulted in estimated CTox value (i.e.: sustained concentration expected to produce toxicity in a 14 day repeat dosing study) of 90 μM for J-147. The CeeTox panel shows that J-147 produced some adverse effects on cellular activities, in particular mitochondrial function, but only with high concentrations of the drug. J-147 was also not genetoxic with or without Aroclor-1254 treatment. For J-147, based upon extensive neuroprotection assay data previously published, and the CeeTox assay (CTox value of 90 μM) in this study, we estimated in vitro neuroprotection efficacy (EC50 range 0.06-0.115 μM)/toxicity ratio is 782.6-1500 fold and the neurotrophism (EC50 range 0.025 μM)/toxicity ratio is 3600, suggesting that there is a significant therapeutic safety window for J-147 and that it should be further developed as a novel neuroprotectiveneurotrophic agent to treat neurodegenerative disease taking into account current National Institute of Neurological Disorders and Stroke (NINDS) RIGOR guidelines.

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