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Discovery and optimization of a novel series of liver X receptor-alpha agonists
Leping Li1, Jiwen Liu, Liusheng Zhu
1Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. leping1@amgen.com
Abstract:
A novel series of hexafluorocarbinols were discovered as potent activators of the liver X receptor-alpha using a fluorescence polarization assay. Structure-activity relationship study led to the identification of compounds that are more potent agonists than the endogenous ligand, 24(S), 25-epoxycholesterol, with similar efficacy. Several compounds, including T0901317, were shown to have desirable pharmacokinetic profiles suitable for in vivo studies.
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