Table 1.
Summary of inhibition data obtained for lerisetron, analog 1 and analog 2 on mutant and wildtype receptors. Ki values were calculated from IC50 values as previously described. All data is the result of n > 4 experiments and is expressed as the mean ± SE. The relative change in Ki was calculated as the Ki (mutant) / Ki (wildtype) and indicates the increase in Ki relative to wildtype ± SE. * indicates significant difference in fold change value. Kd values for [3H]granisetron binding to wt and mutant receptors were reproduced from reference 25.
| Ligand | [3H] Granisetron | Lerisetron | Analog 1 | Analog 2 | ||||
| Amino acid | Kd (nM) | Fold change | Ki (nM) | Fold change | Ki (nM) | Fold change | Ki (nM) | Fold change |
| WT | 0.98 ± 0.12 | 1 | 0.8 ± 0.19 | 1 | 25 ± 3.2 | 1 | 320 ± 82 | 1 |
| W89F | 5.7 ± 0.7 | 5.8 ± 0.7 | 3.8 ± 0.46 | 4.8 ± 0.56* | 170 ± 54 | 7.0 ± 3.2* | 1600 ± 400 | 5.1 ± 1.3* |
| W89Y | 18 ± 2.0 | 18 ± 2.1 | 2.8 ± 0.14 | 3.5 ± 0.38* | 81 ± 14 | 3.2 ± 0.6* | 2200 ± 520 | 6.8 ± 1.6* |
| R91A | 4.9 ± 0.7 | 5 ± 0.8 | 6.1 ± 1.16 | 7.6 ± 1.45* | 22.7 ± 8 | 0.9 ± 0.28 | 180 ± 27 | 0.56 ± 0.14 |
| Y140A | 2.7 ± 0.2 | 2.8 ± 0.3 | 2.1 ± 0.33 | 2.6 ± 0.37 | 88 ± 45 | 3.5 ± 1.7 | 470 ± 210 | 1.4 ± 0.65 |
| Y142A | 4.5 ± 0.5 | 4.6 ± 0.5 | 130 ± 28 | 160 ± 37 | 170 ± 58 | 6.8 ± 2.3* | 5500 ± 240 | 17 ± 0.77 |
| Y152A | 7.8 ± 1.1 | 8 ± 1.1 | 150 ± 36 | 190 ± 43 | 2500 ± 400 | 98 ± 16 | 13000 ± 4200 | 40 ± 12 |