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

Authors

  • Ali Dabbagh Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences,Tehran, Iran.
  • Ali Golchin Dpartment of Tissue Engineering and Applied Cell, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Hakimeh Zali Dpartment of Tissue Engineering and Applied Cell, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Masoumeh Farahani Proteomics Research Center, Faculty of paramedical science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Mohammad Mehdi Ranjbar Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran.
  • Mohsen Yazdani Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran.
Abstract:

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.

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Journal title

volume 18  issue 3

pages  1639- 1647

publication date 2019-07-01

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