In Silico Identification of New Inhibitors of the LOX-1 Receptor via Molecular Docking, ADMET Pharmacokinetics and Molecular Dynamics Simulations

Research focusing on targeting the LOX-1 receptor has gained increasing interest because of its established role in the development of cancer and arteriosclerotic diseases, which are among the main causes of human death. In this study, we employed an in silico approach involving molecular docking and molecular dynamics simulations to identify and characterize novel compounds that can target LOX-1 receptors under safe conditions. The results indicated that smilagenin was the compound with the best binding affinity for LOX-1, followed by cannabinol and prasterone. Analysis of protein‒ligand interactions suggested that smilagenin is the most stable of all the selected compounds and that it exhibited a different binding mode to the LOX-1 receptor than the other compounds did. Furthermore, analysis of their pharmacological properties revealed that smilagenin is the safest drug, followed by cannabinol. Moreover, the all-atom molecular dynamics simulation revealed that all the selected compounds are globally stable. These results provide new data on molecules that can target LOX-1 receptors via their respective binding modes. According to this study, all three compounds could be suitable candidates for targeting LOX-1 to treat cancer and arteriosclerosis, especially cannabinol, which showed the most promising results. However, further studies need to be performed to validate these results.