TABLE 2.
Affinity estimates (pKB) for mGlu5 NAMs from functional assays
Collated data were fitted to the operational model of allosterism. Data represented as means ± S.E.M. from the indicated number (n) of independent experiments performed in triplicate.
| Ca2+ mobilization | IP1 accumulation | ERK1/2 phosphorylation | Receptor internalization | |||||
|---|---|---|---|---|---|---|---|---|
| pKB | n | pKB | n | pKB | n | pKB | n | |
| AZD2066 | 6.49 ± 0.15 | 3 | 7.82 ± 0.12 | 4 | 7.34 ± 0.14 | 3 | 6.75 ± 0.14 | 3 |
| Basimglurant | 8.33 ± 0.15 | 3 | 8.69 ± 0.13 | 4 | 8.66 ± 0.15 | 4 | 8.06 ± 0.12a | 3 |
| Dipraglurant | 5.83 ± 0.15 | 3 | 6.50 ± 0.12b | 4 | 6.67 ± 0.14b | 3 | 7.17 ± 0.13a,b | 3 |
| F169521 | 6.09 ± 0.15 | 3 | 6.19 ± 0.15 | 4 | 6.69 ± 0.14 | 3 | 6.24 ± 0.12 | 3 |
| F1699611 | 6.25 ± 0.15 | 3 | 7.08 ± 0.12b | 4 | 6.82 ± 0.14 | 3 | 6.71 ± 0.13 | 3 |
| Mavoglurant | 6.49 ± 0.15 | 3 | 7.55 ± 0.11b | 4 | 7.30 ± 0.14b | 3 | 7.04 ± 0.13 | 3 |
| Remeglurant | 6.09 ± 0.15 | 3 | 7.12 ± 0.12b | 4 | 7.09 ± 0.14b | 3 | 6.79 ± 0.13b | 3 |
| (RS)-remeglurant | 5.80 ± 0.15 | 3 | 6.54 ± 0.13b | 4 | 7.04 ± 0.13b | 3 | 6.33 ± 0.13c | 3 |
| STX107 | 6.97 ± 0.15 | 3 | 7.46 ± 0.11 | 4 | 7.52 ± 0.14 | 3 | 7.14 ± 0.19 | 3 |
a
Significantly different from estimate derived from IP1 accumulation assays, P < 0.05, one-way ANOVA with Tukey’s multiple comparisons post-test.
b
Significantly different from estimate derived from Ca2+ mobilization assays, P < 0.05, one-way ANOVA with Tukey’s multiple comparisons post-test.
c
Significantly different from estimate derived from ERK1/2 phosphorylation assays, P < 0.05, one-way ANOVA with Tukey’s multiple comparisons post-test.