Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia

…, C Desroches, X Du, R Gordon, J Guay…

Index: Oballa, Renata M.; Belair, Liette; Black, W. Cameron; Bleasby, Kelly; Chan, Chi Chung; Desroches, Carole; Du, Xiaobing; Gordon, Robert; Guay, Jocelyne; Guiral, Sebastien; Hafey, Michael J.; Hamelin, Emelie; Huang, Zheng; Kennedy, Brian; Lachance, Nicolas; Landry, France; Li, Chun Sing; Mancini, Joseph; Normandin, Denis; Pocai, Alessandro; Powell, David A.; Ramtohul, Yeeman K.; Skorey, Kathryn; Sorensen, Dan; Sturkenboom, Wayne; Styhler, Angela; Waddleton, Deena M.; Wang, Hao; Wong, Simon; Xu, Lijing; Zhang, Lei Journal of Medicinal Chemistry, 2011 , vol. 54, # 14 p. 5082 - 5096

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Citation Number: 60

Abstract

The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ ...