The Inhibition Mechanism of Pancreatic Ductal Adenocarcinoma via LXR Receptors: A Multifaceted Approach Integrating Molecular Docking, Molecular Dynamics and Post-MD Inter-Molecular Contact Analysis

Abstract

Objective: Pancreatic ductal adenocarcinoma (PDAC) has an unfavorable outlook due to its aggressive characteristics, delayed diagnosis, and limited effective treatment options for advanced stages of the disease. The significant mortality rate has prompted investigations into additional factors that could aid in managing this type of cancer. Liver X receptors, specifically LXRα and LXRβ, are nuclear receptors that oversee the expression of genes related to cholesterol, glucose, lipid metabolism, and inflammatory responses. LXRs have also emerged as potential targets for addressing PDAC, and recent findings have demonstrated that LXR ligands can impede cell proliferation in various cancer forms, notably pancreatic cancer. This comprehensive computational research study involving oncological in silico mechanism discovery explored inhibitory ligands for Liver X receptors (LXRα and LXRβ), which are believed to have prognostic significance in PDAC. Methods: The study utilized Baicalein, Beta-Sitosterol, Polydatin ligands in molecular docking and dynamics and post-molecular Hydrogen bonding contact analyses dynamics to characterize receptor inhibition. Result: The outcomes suggest that Baicalein exhibits versatile inhibitory effects on both receptors, while Beta-Sitosterol emerges as a highly effective inhibitor of LXRβ. Conclusion: Further in vitro and in vivo investigations will be beneficial and would shed light onto the mechanism to decipher the suppression of PDAC evaluating the potential of Baicalein, Beta-Sitosterol, Polydatin natural ligand compounds.