Table 1.
Comparison of icatibant and MEN16132 affinity at wild type and mutant human B2 receptors (hB2R)
| [3H]-bradykinin binding | |||||
|---|---|---|---|---|---|
| MEN16132 | Icatibant | ||||
| hB2R | TM | Ki[nM] (95% CI) | Fmut | Ki[nM] (95% CI) | Fmut |
| Wild type | 0.09 (0.07–0.10) | 1 | 0.08 (0.07–0.09) | 1 | |
| E47A | 1 | 0.15 (0.12–0.18) | 1.6 | 0.19 (0.16–0.25) | 2.4 |
| I110A | 3 | 28 (19–41) | 311 | 0.25 (0.22–0.39) | 3.1 |
| S111A | 3 | 0.11 (0.085–0.14) | 1.2 | 0.16 (0.09–0.31) | 2 |
| L114A | 3 | 0.10 (0.09–0.11) | 1.1 | 0.11 (0.08–0.13) | 1.4 |
| S117A | 3 | 0.15 (0.11–0.20) | 1.7 | 0.19 (0.14–0.23) | 2.3 |
| T158A | 4 | 0.09 (0.075–0.11) | 1 | 0.12 (0.06–0.22) | 1.5 |
| L166F | 4 | 0.11 (0.09–0.14) | 1.2 | 0.15 (0.12–0.20) | 1.8 |
| F252A | 6 | 0.18 (0.15–0.23) | 2 | 0.02 (0.01–0.05) | 0.2 |
| W256A | 6 | 0.44 (0.37–0.51) | 5 | 0.16 (0.14–0.20) | 2 |
| Q288A | 7 | 0.15 (0.10–0.21) | 1.7 | 0.25 (0.19–0.40) | 3.1 |
| F292A | 7 | 0.22 (0.17–0.29) | 2.4 | 0.11 (0.12–0.25) | 1.4 |
| Y295F | 7 | 9.0 (7.9–10.5) | 100 | 0.39 (0.31–0.51) | 4.9 |
| Y295A | 7 | 68 (56–83) | 755 | 0.15 (0.06–0.38) | 1.9 |
| Y295W | 7 | 2.7 (2.4–3.5) | 30 | 0.07 (0.04–0.15) | 0.9 |
| W256A/Y295F | 6/7 | 151 (116–197) | 1670 | 0.35 (0.17–0.71) | 4.4 |
The affinity was evaluated at the peptide agonist [3H]-bradykinin radioligand binding site. Fmut index was calculated as Ki (mutant receptor)/Ki (wild type receptor), and corresponds to fold decrease in affinity. Fmut indexes greater than 3 are shown in bold type. TM indicates the transmembrane portion of the receptor where the mutated amino acid residue is located. Data are from three independent experiments, each one performed in duplicate. Ki values measured for MEN16132 were previously presented (Cucchi et al., 2005).