eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2024-09-30 17 3 1499 1522 10.13005/bpj/2960 61373 article Sarder Arifuzzaman 1 Zubair Khalid Labu 1 Md. Harun -Or- Rashid 1 Farhina Rahman Laboni 1 Mst. Reshma Khatun 2 Md Sajib Ali 2 Department of Pharmacy, World University of Bangladesh, Uttara, Dhaka, Bangladesh Department of Pharmacy, Manarat International University, Ashulia, Dhaka, Bangladesh Studies have demonstrated the association between LXR activity dysregulation with many diseases, including atherosclerosis, diabetes and cancer. In recent years, several LXR agonists have surfaced, but none have been approved for human use due to adverse effects or unforeseen reasons. In this study, we first analysed the mRNA and protein expression of LXRs across tissues, network and pathway analysis, and reinterpreted their physiological function and disease association by utilizing multiple biological data repositories, including RNA-seq human protein atlas, DisGeNET, etc. Then, we performed ligand-based virtual screening, chemico-pharmacokinetic analysis, docking and simulation to identify potential new compounds. Our findings of mRNA, protein expression, network and disease enrichment analysis reveal diverse physiological functions of LXRs addressing the possibility of pharmacological manipulation with small molecules would provide therapeutic strategies for disease management. Evaluation of the docking and chemico-pharmacokinetic properties directed to the selection of LXR-623 and AZ876 as promising candidates for LXR-α and LXR-β for further in-silico investigation. Comprehensive screening for new ligands targeting LXRs based on the chemical structures of LXR-623 and AZ876, identified ZINC000005399501 and ZINC000021912941 with the highest binding affinity (−9.8 and −10.7 kcal/mol) for LXRα and LXRβ, respectively. Our results also supported in simulation study, along with favorable chemico-pharmacokinetic features. https://biomedpharmajournal.org/vol17no3/identification-of-novel-compounds-targeting-the-liver-x-receptor-lxr-in-silico-studies-screening-molecular-docking-and-chemico-pharmacokinetic-analysis/ Agonists Atherosclerosis Chemico-Pharmacokinetic Docking LXRs Metabolic Disease Virtual Screening