Identification of phenylsulfone-substituted quinoxaline (WYE-672) as a tissue selective liver X-receptor (LXR) agonist

…, IB Feingold, AG Nilsson, A Wilhelmsson…

Index: Hu, Baihua; Unwalla, Rayomand J.; Goljer, Igor; Jetter, James W.; Quinet, Elaine M.; Berrodin, Thomas J.; Basso, Michael D.; Feingold, Irene B.; Nilsson, Annika Goos; Wilhelmsson, Anna; Evans, Mark J.; Wrobel, Jay E. Journal of Medicinal Chemistry, 2010 , vol. 53, # 8 p. 3296 - 3304

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Citation Number: 28

Abstract

A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXRβ in kidney HEK-293 cells but did not activate Gal4 LXRβ fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXRβ (IC50= 53 nM), it had little binding affinity for LXRα (IC50> 1.0 μM) and did not recruit any coactivator/ ...