Nicotinic acids: Liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy

…, D Deschenes, M Gagnon, R Gordon, J Guay…

Index: Powell, David A.; Black, W. Cameron; Bleasby, Kelly; Chan, Chi-Chung; Deschenes, Denis; Gagnon, Marc; Gordon, Rob; Guay, Jocelyne; Guiral, Sebastien; Hafey, Michael J.; Huang, Zheng; Isabel, Elise; Leblanc, Yves; Styhler, Angela; Xu, Li-Jing; Zhang, Lei; Oballa, Renata M. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 24 p. 7281 - 7286

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Citation Number: 15

Abstract

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 ...