FDA approved drugs repurposing of Toll-like receptor4 (TLR4) candidate for neuropathy

摘要

Accumulating evidence indicates that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and are definitively involved in the expansion and maintenance of the neuropathic pain. However, the application of docking in virtual-screening in silico methods to drug discovery has some challenge but it allows us to make the directed and meaningful design of drugs for a target protein, which can be shortening and low costing the evolution and discovery of very promising lead new drugs. Nevertheless, in parallel with virtual screening methods, attendant developments in cell culture and in vivo studies must be achieved. In the present paper, we aimed to discover new drugs that have the ability to bind and inhibit TLR4 functions. So, after using the Pathway studio to investigate the biological pathways and protein interaction maps between TLR4 and neuropathy, we reported the application of the affinity-based approach of different pharmaceuticals; these agents contained all of the approved drugs; which could bind to Toll-like receptor 4 in blind high-throughput in silico screening. Our results demonstrated that among the primary list of 1945 retrieved compounds, 39 approved compounds could be the right candidate to perform a biological test in different in vivo and in vitro conditions and as a lead for further neurophysiological and neuropathological studies and treatment of neuropathic pain.