Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition

Saqib U., Savai R., Liu D., Banerjee S., Baig M. S.

JOURNAL OF CELLULAR BIOCHEMISTRY, vol.120, no.2, pp.1522-1526, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 120 Issue: 2
  • Publication Date: 2019
  • Doi Number: 10.1002/jcb.27334
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1522-1526
  • Middle East Technical University Affiliated: Yes


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.