Conversion of human-selective PPARα agonists to human/mouse dual agonists: a molecular modeling analysis

…, A Kunkel, DE Mais, C Montrose-Rafizadeh…

Index: Wang, Minmin; Winneroski, Leonard L.; Ardecky, Robert J.; Babine, Robert E.; Brooks, Dawn A.; Etgen, Garret J.; Hutchison, Darrell R.; Kauffman, Raymond F.; Kunkel, Aaron; Mais, Dale E.; Montrose-Rafizadeh, Chahrzad; Ogilvie, Kathleen M.; Oldham, Brian A.; Peters, Mary K.; Rito, Christopher J.; Rungta, Deepa K.; Tripp, Allie E.; Wilson, Sarah B.; Xu, Yanping; Zink, Richard W.; McCarthy, James R. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 24 p. 6113 - 6116

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Citation Number: 9

Abstract

To understand the species selectivity in a series of α-methyl-α-phenoxy carboxylic acid PPARα/γ dual agonists (1–11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARα. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARα leads to the species-specific divergence in ligand binding. ...