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ID: ALA1949499

Journal: Bioorg Med Chem Lett

Title: Nicotinic acids: liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy.

Authors: Powell DA, Black WC, Bleasby K, Chan CC, Deschenes D, Gagnon M, Gordon R, Guay J, Guiral S, Hafey MJ, Huang Z, Isabel E, Leblanc Y, Styhler A, Xu LJ, Zhang L, Oballa RM.

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 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.

CiteXplore: 22047692

DOI: 10.1016/j.bmcl.2011.10.040