In Silico Molecular Docking Analysis of Valproic Acid as an Inhibitor of Bruton's Tyrosine Kinase: Potential Drug Repurposing for Allergies.

Mast cells (MCs) participate in inflammation and pathological processes such as type I hypersensitivity. They can recognize type E immunoglobulins (IgE)-coupled allergens through the high-affinity receptors for IgE (FcεRI) membrane receptor, inducing the activation of a signaling pathway in which molecules such as spleen tyrosine kinase (SyK), Bruton's tyrosine kinase (BTK), and phospholipase Cy2 (PLCγ2) participate, promoting MC degranulation by promoting calcium mobilization. Valproic acid (VPA) selectively decreases PLCγ2 phosphorylation without impacting SyK kinase activity. Although BTK acts in parallel to SyK by phosphorylating PLCγ2, it has not been demonstrated whether VPA directly affects BTK. For this reason, the purpose of this work is to evaluate the interaction of BTK with VPA in an in silico molecular coupling analysis. Three-dimensional (3D) models of the ligand and receptor were selected to evaluate coupling with the support of bioinformatics tools, compared with a reference drug. Our results indicate that VPA binds favorably to BTK near its catalytic site. This binding is distinct from irreversible inhibitors, suggesting its role as a reversible inhibitor of this enzyme.