Table 1.
Functional affinity (pK B) and cooperativity (Logαβ) parameters for CaS receptor modulators determined in Ca2+ i mobilisation assays, as described
| Ronacaleret | ATF936 | Pfizer compound 1 | BMS compound 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pK B | Logαβ (αβ) | n | pK B | Logαβ (αβ) | n | pK B | Logαβ (αβ) | n | pK B | Logαβ (αβ) | n | |
| WT | 6.35 ± 0.09 | −1.56 ± 0.16 (0.03) | 6 | 7.59 ± 0.10 | −2.30 ± 0.15 (0.005) | 6 | 7.82 ± 0.14 | −2.03 ± 0.13 (0.009) | 5 | 6.97 ± 0.07 | −1.47 ± 0.05 (0.03) | 12 |
| F6682.56A | NA | NA | 4 | 7.76 ± 0.09 | −2.37 ± 0.16 (0.004) | 5 | 7.35 ± 0.14 | −1.34 ± 0.13* (0.05) | 5 | 7.26 ± 0.12 | −2.08 ± 0.13* (0.008) | 5 |
| G670ECL1A | 6.90 ± 0.08* | −1.29 ± 0.05 (0.05) | 5 | 8.21 ± 0.05* | −2.61 ± 0.08 (0.002) | 5 | 8.27 ± 0.05 | −2.17 ± 0.05 (0.007) | 5 | 6.87 ± 0.09 | −1.58 ± 0.08 (0.03) | 5 |
| R6803.32A | NA | NA | 3 | 7.56 ± 0.10 | −1.90 ± 0.13 (0.01) | 5 | 6.67 ± 0.19* | −0.97 ± 0.10* (0.11) | 5 | 6.73 ± 0.10 | −1.12 ± 0.07 (0.08) | 5 |
| F6843.36A | NA | NA | 3 | NA | NA | 3 | NA | NA | 4 | 6.70 ± 0.10 | −2.02 ± 0.32* (0.009) | 5 |
| F6883.40A | NA | NA | 3 | NA | NA | 3 | NA | NA | 4 | 6.70 ± 0.10 | −1.92 ± 0.27 (0.01) | 5 |
| E767ECL2A | 6.43 ± 0.12 | −1.17 ± 0.11 (0.07) | 5 | 8.24 ± 0.09* | −3.35 ± 0.27* (0.0004) | 5 | 8.33 ± 0.09* | −2.55 ± 0.10* (0.003) | 5 | 7.88 ± 0.11* | −2.32 ± 0.12* (0.005) | 5 |
| W8186.50A | 7.94 ± 0.07* | −1.96 ± 0.06 (0.01) | 5 | 5.78 ± 0.26* | −0.52 ± 0.12* (0.30) | 5 | 7.39 ± 0.07 | −2.29 ± 0.13 (0.005) | 5 | 7.32 ± 0.12 | −1.12 ± 0.07 (0.08) | 5 |
| F8216.53A | NA | NA | 4 | NA | NA | 4 | NA | NA | 4 | NA | NA | 4 |
| Y8256.56A | NA | NA | 3 | 7.18 ± 0.10 | −1.90 ± 0.14 (0.01) | 5 | 7.91 ± 0.07 | ~ − 100 | 5 | 6.82 ± 0.09 | −1.93 ± 0.15 (0.01) | 5 |
| E8377.32I | NA | NA | 3 | 7.97 ± 0.09 | −2.18 ± 0.12 (0.007) | 5 | 6.44 ± 0.12* | −1.17 ± 0.09* (0.07) | 5 | 6.06 ± 0.11* | −1.31 ± 0.20 (0.05) | 5 |
| I8417.36A | NA | NA | 4 | 6.64 ± 0.11* | −1.24 ± 0.11* (0.06) | 5 | 6.62 ± 0.15* | −0.88 ± 0.07* (0.13) | 5 | 6.50 ± 0.13* | −1.37 ± 0.11 (0.04) | 6 |
Note. Data are mean ± SEM from the indicated number of independent experiments (n). NA denotes not determined due to no or weak modulator activity.
*
P < .05, significantly different from WT; one‐way ANOVA with Dunnett's multiple comparisons post test.