Table 1.
Biological activity evaluation (i.e. agonism, through Ca2+ mobilisation) of selected ligands for FPR1 and FPR2 in HL-60 and RBL-2H3 transfected cells
| na | Ca2+ mobilisation—EC50, μM; efficacy (%)b | Conclusion on the basis of EC50 results in HL-60 cells | Conclusion on the basis of EC50 results in RBL-2H3 cells | |||
|---|---|---|---|---|---|---|
| HL-60 cellsc | RBL-2H3 cellsd | |||||
| FPR1 | FPR2 | FPR1 | FPR2 | |||
| 14d 2 | 2.6 (110) | 4.0 (35) | 44.7 | 21.1 | Active for FPR1 and FPR2 | LA for FPR1 and FPR2 |
| 14e 2 | 2.8 (90) | 6.8 (40) | NA | 1.8 (70) | Active for FPR1 and FPR2 | Selective/active for FPR2 |
| 14f 2 | 7.6 (40) | NA | NA | NA | Selective for FPR1 | NA |
| 14j 2 | 7.7 (65) | 14.4 (35) | 1.8 (70) | NA | Active for FPR1/MA for FPR2 | Selective for FPR1 |
| 14l 2 | 15.5 (25) | 16.8 (25) | NA | 51.4 | MA for FPR1 and FPR2 | Selective (LA) for FPR2 |
| 14m 2 | 2.3 (50) | NA | 33.2 | NA | Selective for FPR1 | Selective (LA) for FPR1 |
| 14n 2 | 5.7 (50) | 8.8 (95) | 36.5 | 51.0 | Active for FPR1 and FPR2 | LA for FPR1 and FPR2 |
| 14p 2 | 10.5 (60) | 12.3 (55) | 35.4 | 38.3 | MA for FPR1 and FPR2 | LA for FPR1 and FPR2 |
| 6d 6 | 10.8 (80) | NA | NA | NA | Selective (MA) for FPR1 | NA |
| 6e 6 | 9.0 (110) | 4.3 (25) | 3.3 (105) | NA | Active for FPR1 and FPR2 | Selective for FPR1 |
| 11j 6 | 4.5 (100) | 14.1 (65) | 1.4 (70) | 2.8 (90) | Active for FPR1/MA for FPR2 | Active for FPR1 and FPR2 |
| 11l 6 | 13.8 (20) | NA | 3.6 (25) | 3.8 (50) | Selective (MA) for FPR1 | Active for FPR1 and FPR2 |
| 17a 2 | 9.7 (30) | 5.4 (25) | NA | 15.1 (75) | Active for FPR1 and FPR2 | Selective (MA) for FPR2 |
| 17b 2 | 3.2 (90) | 1.9 (20)e | 1.6 (100) | 3.2 (60) | Active for FPR1 and FPR2 | Active for FPR1 and FPR2 |
| 33 6 | 11.2 (55) | NA | 6.3 (100) | 2.1 (45) | Selective (MA) for FPR1 | Active for FPR1 and FPR2 |
NA no activity (on the basis of the limits of EC50 < 50 μM and efficacy ≥ 20%), LA low active (i.e. EC50 > 20 μM), MA moderate active (i.e. 10 μM ≤ EC50 ≤ 20 μM)
a Ligand numbers match the original numbers2, 6; for experimental details see in refs. 2 and 6
b Efficacy (in parentheses) is expressed as % of the response induced by 5 nM fMLF (FPR1) or 5 nM WKYMVm (FPR2) and is calculated only for ligands with EC50 < 30 μM
c Previously reported potency of the ligands evaluated in HL-60 cells2, 6
d See ref. 10 for experimental details, i.e. potency of the ligands in RBL-2H3 cells, measured through the collaboration with M.P. Giovannoni (University of Florence) and M.T. Quinn (Montana State University)
e Potency of compound 17b for FPR2 in HL-60 cells. Due to the low efficacy (i.e. ≤ 20%, chosen cut-off for affinity)2, 3, 6, the ligand (as racemic mixture) has been considered a selective agonist for FPR12