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Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition
Date
2019-02-01
Author
Saqib, Uzma
Savai, Rajkumar
Liu, DongFang
Banerjee, Sreeparna
Baig, Mirza S.
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
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Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. It has been linked to various pathologies, including pain and inflammation. Several peptide and peptidomimetic agonizts for PAR-2 have been developed exhibiting high potency and efficacy. However, the number of PAR-2 antagonists is smaller. We screened the Food and Drug Administration library of approved compounds to retrieve novel antagonists for repositioning in the PAR-2 structure. The most efficacious compound bicalutamide bound to the PAR-2 binding groove near the extracellular domain as observed in the in silico studies. Further, it showed reduced Ca2+ release in trypsin activated cells in a dose-dependent manner. Hence, bicalutamide is a novel and potent PAR-2 antagonist which could be therapeutically useful in blocking multiple pathways diverging from PAR-2 signaling. Further, the novel scaffold of bicalutamide represents a new molecular structure for PAR-2 antagonism and can serve as a basis for further drug development.
Subject Keywords
Cell Biology
,
Biochemistry
,
Molecular Biology
URI
https://hdl.handle.net/11511/34865
Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
DOI
https://doi.org/10.1002/jcb.27334
Collections
Department of Biology, Article
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BibTeX
U. Saqib, R. Savai, D. Liu, S. Banerjee, and M. S. Baig, “Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition,”
JOURNAL OF CELLULAR BIOCHEMISTRY
, pp. 1522–1526, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/34865.