Extended Data Table 1 Structures, pharmacology and binding data for PAR2 antagonists

From: Structural insight into allosteric modulation of protease-activated receptor 2

  1. Weak antagonists of PAR2 were identified by high-throughput screening (AZ7188), and further optimization resulted in AZ8838, a selective PAR2 antagonist. The chemotype of compound AZ3451 was identified by screening DNA-encoded libraries on purified, PAR2-StaR. The series were optimized resulting in a potent antagonist AZ3451. All potencies for IP-One and FLIPR were measured in 1321N1 cells overexpressing wild-type human PAR2 and are reported as mean ± s.e.m. Stimulation of these cells with SLIGRL also resulted in phosphorylation of extracellular signal-regulated kinase (ERK) detected using phospho-T202/Y204 kit (Cisbio), with no effect in parental cells. At EC80 of activating peptide (8 μM) both compounds AZ8838 and AZ3451, when individually added to cells at 10 μM, were able to completely inhibit ERK phosphorylation (not shown). No agonist activity was observed for the listed compounds.
  2. 1Pathhunter recruitment assay at DiscoverX with activation of the receptor using isoform-specific activating peptide.
  3. 2nd = not determined.