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+ mobilizationIP1 accumulationERK1/2 phosphorylationReceptor internalization
pKBnpKBnpKBnpKBn
AZD20666.49 ± 0.1537.82 ± 0.1247.34 ± 0.1436.75 ± 0.143
Basimglurant8.33 ± 0.1538.69 ± 0.1348.66 ± 0.1548.06 ± 0.12a3
Dipraglurant5.83 ± 0.1536.50 ± 0.12b46.67 ± 0.14b37.17 ± 0.13a,b3
F1695216.09 ± 0.1536.19 ± 0.1546.69 ± 0.1436.24 ± 0.123
F16996116.25 ± 0.1537.08 ± 0.12b46.82 ± 0.1436.71 ± 0.133
Mavoglurant6.49 ± 0.1537.55 ± 0.11b47.30 ± 0.14b37.04 ± 0.133
Remeglurant6.09 ± 0.1537.12 ± 0.12b47.09 ± 0.14b36.79 ± 0.13b3
(RS)-remeglurant5.80 ± 0.1536.54 ± 0.13b47.04 ± 0.13b36.33 ± 0.13c3
STX1076.97 ± 0.1537.46 ± 0.1147.52 ± 0.1437.14 ± 0.193
  • 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.