LXRα agonist 40 is a potent, specific agonist of transcription factor liver X receptor alpha (LXRα) with EC50 of 42 nM in TR-FRET assays, 6.3 fold selective over LXRβ activation.
LXRα agonist 40 shows strong cellular activity and selectivity for LXRα (EC50=27 nM), 23-fold lower than that for LXRβ (EC50=631 nM) in HCC cells.
LXRα agonist 40 shows no activity against nuclear receptors that are either known to directly or indirectly regulate metabolic processes in the liver, including vitamin D receptor (VDR), PPAR α/γ, estrogen receptor α and β (ERα and β) and farnesoid X receptor (FXR) or aryl hydrocarbon receptor (AhR) and the mice constitutive androstane receptor (mCAR).
LXRα agonist 40 triggers cell death, oxidative stress, and an ER stress response in HCC cells in combination with an DFG-out Raf inhibitor, strongly reduces the cell viability of Hep3B cells in combination with sorafenib with EC50 of 1.7 uM.
LXRα agonist 40 is highly efficient in HCC organoids in combination with sorafenib but not in healthy liver cells.