Abstract
Toll-like receptor (TLR) 7 has an important role in immune activation processes and represents an emerging drug discovery target for the development of immunomodulators. Three-dimensional similarity-based virtual screening was performed using the Rapid Overlay of Chemical Structures software (vROCS version 3.1.1. OpenEye Scientific Software, Santa Fe, NM. http://www.eyesopen.com) to search for potential ligands of TLR7. Six new compounds with three new chemical scaffolds were discovered as initial hit antagonists of TLR7, with IC50 values in the micromolar range, as determined by reporter assays. With only the imidazoquinolines described as small-molecule TLR7 antagonists to date, the new chemotypes described in this report represent an important starting point for the development of drug candidates for treatment of autoimmune diseases.
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Acknowledgments
We thank OpenEye Scientific Software, Santa Fe, NM, USA, for free academic licenses for the use of their software, and Dr. Chris Berrie for critical reading of the manuscript. The financial support of the Slovenian Research Agency is gratefully acknowledged.
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Švajger, U., Horvat, Ž., Knez, D. et al. New antagonists of toll-like receptor 7 discovered through 3D ligand-based virtual screening. Med Chem Res 24, 362–371 (2015). https://doi.org/10.1007/s00044-014-1127-5
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DOI: https://doi.org/10.1007/s00044-014-1127-5