Drug repurpose screening identifies regorafenib as potential amyloid‐beta aggregation inhibitor
Blake Eby, Skye Chaapel, Evan Kasper, Gabriella Mancini, Isaiah Miller, Liam Fisher, Carmen McKell, Paul A Martino · Alzheimer s & Dementia · 2022
Abstract Background Regorafenib is an FDA‐approved multikinase inhibitor used to treat cancer. Drug repurposing may allow for indications as an Alzheimer’s therapeutic targeting inhibition of amyloid‐beta aggregation. Method Regorafenib was one of several FDA‐approved drug candidates uncovered in a literature search. Initial in‐silico tests implemented [AutoDock Vina] to model the peptide‐ligand interactions between regorafenib and amyloid‐beta. Thioflavin T assays were used to measure regorafenib’s impact on amyloid‐beta aggregation relative to other small molecule candidates. Circular dichroism spectroscopy was performed to determine the dose‐response impact of regorafenib. Result Computational analysis revealed strong binding between regorafenib and amyloid‐beta 42. Aggregation assays and CD spectroscopy data provide evidence for the effectiveness of regorafenib as an amyloid‐beta aggregation inhibitor. Conclusion Regorafenib inhibits amyloid‐beta 42 aggregation and may be repurposed as an Alzheimer’s Disease therapeutic. The structural activity of regorafenib as a kinase inhibitor could be used as a model for future drug repurposing.