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

Uzma Saqib, Rajkumar Savai, Dong Fang Liu, Sreeparna Banerjee, Mirza S. Baig

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1522-1526
Number of pages5
JournalJournal of Cellular Biochemistry
Issue number2
StatePublished - Feb 2019


  • antagonist
  • drug repositioning
  • inflammation
  • proteinase-activated receptor 2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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