NDLI: CMX-2043 Mechanisms of Action In Vitro.

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CMX-2043 Mechanisms of Action In Vitro.

Content Provider	Semantic Scholar
Author	Lader, Alan S. Baguisi, Alexander B. Casale, Ralph A. Kates, Steven A. Beeuwkes, Reinier
Copyright Year	2016
Abstract	α-Lipoic acid has been shown to provide cytoprotection in some tissues through antioxidant and antiapoptotic mechanisms. We have enhanced these properties by synthetic modification, resulting in a new chemical entity, CMX-2043, with proven efficacy in an animal model of cardiac ischemia-reperfusion injury. The present studies compare cytoprotective cellular pathways of R-α-lipoic acid and CMX-2043. Biochemical and cellular assays were used to compare antioxidant potency, tyrosine kinase activation, and protein kinase B (Akt) phosphorylation. CMX-2043 was more effective than lipoic acid in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. Activation of insulin-like growth factor 1 receptor was similar for both. CMX-2043 stimulation of Akt phosphorylation was abolished by the phosphatidylinositide 3-kinase inhibitor LY294002. Consistent with Akt activation, CMX-2043 reduced carbachol-induced calcium overload. The S-stereoisomer of CMX-2043 was less active in the biochemical assays than the R-isomer. These results are consistent with cytoprotection through activation of Akt and antioxidant action. CMX-2043 may thus provide a pharmacological approach to cytoprotection consistent with established anti-apoptotic mechanisms.
File Format	PDF HTM / HTML
DOI	10.1097/FJC.0000000000000408
Alternate Webpage(s)	http://www.ischemix.com/pdf/CMX-2043%20Mechanisms%20of%20Action%20In%20Vitro.pdf
PubMed reference number	27195653
Alternate Webpage(s)	https://doi.org/10.1097/FJC.0000000000000408
Journal	Medline
Volume Number	68
Issue Number	3
Journal	Journal of cardiovascular pharmacology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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