Liver X receptors (LXRs) are nuclear receptors that serve as lipid-responsive transcription factors and exist as two isoforms in the body, LXRα and LXRβ. Further, LXRs are mainly available in the liver and brain. LXRα is highly abundantly expressed in the liver, when compared to LXRβ. Conversely, in the brain, LXRβ is five times more abundant in expression than LXRα. Recently, LXR agonist are famous for the treatment of atherosclerosis because they are involved in the reverse cholesterol transport (RCT) from macrophages by increasing expression of ApoE and cholesterol efflux transporters ABCA1 and ABCG1. However, current LXR full agonist (GW3965 and T0901317) have been shown to increase liver and plasma triglycerides and Low-Density Lipoprotein (LDL). Recent reports have indicated that LXR is highly significant in the brain for lipidation of ApoE and formation of the ApoE-Aβ complex, which results in the clearance of Aβ in the brain. Targeting LXRβ is beneficial in the brain, as it will increase the clearance of Aβ. Our goal is to design and develop novel LXRβ agonists that target the brain without inducing liver steatosis. To validate LXR activity, we tested LXR full agonist (GW3965 and T0901317) using lipid accumulation assay in HEPG2 cells. GW3965 and T0901317 displays increase of lipid accumulation in HEPG2 cells when compared to control. Our lead compound, AU-418LA, was designed computationally with an emphasis on ADME using Schrodinger and GastroPlus modeling software. Our in-silico design was formulated around diminishing interactions with the Arg-305 (LXRα) and Arg-319 (LXRβ) as stabilizing residue and AF2 binding domain (Leu-435, Leu-439, Trp-443 in LXRα and Leu-449, Leu-453, Trp-457 in LXRβ) which are responsible for full activation that leads to lipid accumulation. Based on the docking score, AU-418LA preferably binds to LXRβ (-10.632) than LXRα (-7.644), compared to full agonist GW3965 with docking score of -15.424 (LXRβ) and -14.588 (LXRα). Our future aims are to synthesize the AU-418LA and series of LXRβ-selective agonists and test them using reporter activity and lipid accumulation assays, and measure interactions of AU-418LA bound to the LXR receptor via the crystal structure