Cell experiment:

HepG2 cells are maintained in minimal essential medium supplemented with 10% FBS and antibiotics. HepG2 cells are then treated for 24 h with GSK2033 followed by assessment of expression of genes by qPCR[2].

Animal experiment:

21-week old male C57BL6 DIO mice are used. Animals are individually housed and fed a high fat diet (60% kcal/fat diet, 20% carbohydrate) for the duration of the experiment that includes GSK2033 administration for 28 days (30 mg/kg, q. d, i. p.). Body weight and food intake are monitored daily[2].

GSK2033 is a LXR antagonist with pIC50s of 7 and 7.4 for LXRα or LXRβ, respectively.

GSK2033 is a LXR antagonist with pIC50s of 7 and 7.4 for LXRα or LXRβ, respectively. GSK2033 dose-dependently suppresses basal transcription in full-length LXRα or full-length LXRβ cotransfection assays with IC50s of 17 nM and 9 nM, respectively. GSK2033 also effectively suppresses the transcription of an ABCA1 driven luciferase reporter dose-dependently displaying IC50s of 52 nM for LXRα and 10 nM for LXRβ. GSK2033 also suppresses the expression of both of fatty acid synthase (FASN) and SREBP1[2].

One month treatment of GSK2033 does not have significant effects on hepatic triglyceride levels. Plasma triglyceride levels are also unaffected by treatment with GSK2033[2].

[1]. Zuercher WJ, et al. Discovery of tertiary sulfonamides as potent liver X receptor antagonists. J Med Chem. 2010 Apr 22;53(8):3412-6. [2]. Griffett K, et al. Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease. Biochem Biophys Res Commun. 2016 Oct 21;479(3):424-428.