Document Detail


Nicotinic acids: Liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy.
MedLine Citation:
PMID:  22047692     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity.
Authors:
David A Powell; W Cameron Black; Kelly Bleasby; Chi-Chung Chan; Denis Deschenes; Marc Gagnon; Rob Gordon; Jocelyne Guay; Sebastien Guiral; Michael J Hafey; Zheng Huang; Elise Isabel; Yves Leblanc; Angela Styhler; Li-Jing Xu; Lei Zhang; Renata M Oballa
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-18
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  -     ISSN:  1464-3405     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Québec, Canada H9H 3L1.
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