| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370133 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
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.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
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,