Table 1.
In vitro pharmacology of PAR2 antagonists.
| Compounds | Ca2+ flux (hPAR2) | Ca2+ flux (rPAR2) | IP1 (hPAR2) | pERK1/2 (hPAR2) | β-arrestin (hPAR2) | Competition Binding (hPAR2) |
|---|---|---|---|---|---|---|
| AZ8935 | 7.7 ± 0.1 (n = 3) | 8.1 ± 0.1 (n = 4) | 6.52 ± 0.04 (n = 6) | 5.9 ± 0.1 (n = 3) | 6.42 ± 0.03 (n = 3) | nd |
| AZ3451 | 8.6 ± 0.1 (n = 30) | 8.5 ± 0.1 (n = 12) | 7.65 ± 0.02 (n = 122) | 6.44 ± 0.03 (n = 3) | 7.06 ± 0.04 (n = 3) | 6.9 ± 0.2 (n = 4) |
| AZ2623 | 8.3 ± 0.1 (n = 26) | 8.3 ± 0.1 (n = 12) | 7.09 ± 0.02 (n = 106) | 6.1 ± 0.1 (n = 3) | 6.31 ± 0.04 (n = 3) | 7.1 ± 0.3 (n = 3) |
| AZ7126 | 8.1 ± 0.2 (n = 4) | 8.3 ± 0.2 (n = 4) | 7.1 ± 0.1 (n = 6) | 6.7 ± 0.1 (n = 3) | 7.2 ± 0.1 (n = 3) | nd |
| AZ8838 | 5.70 ± 0.02 (n = 33) | 5.3 ± 0.1 (n = 15) | 5.84 ± 0.02 (n = 158) | 5.7 ± 0.1 (n = 3) | 6.1 ± 0.1 (n = 3) | 5.2 ± 0.1 (n = 3) |
| AZ0107 | 6.1 ± 0.1 (n = 3) | 5.5 ± 0.1 (n = 4) | 6.7 ± 0.1 (n = 12) | 5.9 ± 0.1 (n = 3) | 6.3 ± 0.1 (n = 3) | 5.4 ± 0.2 (n = 3) |
In functional assays, PAR2 was activated with peptide, SLIGRL-NH2 in 1321N1-hPAR2 cells (Ca2+ and IP1) or U2OS-hPAR2 (pERK1/2 and β-arrestin-2). Species differences were considered through monitoring Ca2+ release by rat PAR2 in KNRK cells. Binding was measured in competition experiments against Eu-tagged-2f-LIGRLO(dtpa)-NH2 on CHO-hPAR2 cells. Data are presented as mean pKi (binding only) or pIC50 ± s.e.m. based on n independent experiments.
nd Not determined.