Table 3. GLP-1R Internalization Concentration Response Parameter Estimates for Chimeric Ligands in HEK293-SNAP-GLP-1R Cellsa.
| DERET |
High Content Microscopy Assay |
|||||
|---|---|---|---|---|---|---|
| pEC50 (M) | Emax (AUC) | log τ/KA (M) | pEC50 (M) | Emax (% internalization) | log τ/KA (M) | |
| GLP-1 | 7.5 ± 0.1 | 46 ± 3 | 7.6 ± 0.1 | 7.8 ± 0.1 | 98 ± 3 | 7.8 ± 0.1 |
| Chi1 | 7.8 ± 0.1 | 45 ± 1 | 7.8 ± 0.1 | 8.2 ± 0.1* | 100 ± 3 | 8.2 ± 0.1* |
| Chi2 | 8.1 ± 0.1* | 38 ± 4 | 8.0 ± 0.1* | 8.2 ± 0.1* | 101 ± 3 | 8.2 ± 0.1* |
| Chi3 | 8.5 ± 0.1* | 38 ± 2 | 8.4 ± 0.1* | 8.4 ± 0.1* | 103 ± 4 | 8.4 ± 0.1* |
| Ex4-ala2 | 8.3 ± 0.1* | 43 ± 2 | 8.5 ± 0.1* | 8.3 ± 0.1* | 101 ± 5 | 8.3 ± 0.1* |
| Ex4 | 8.2 ± 0.0* | 39 ± 2 | 8.3 ± 0.1* | 8.4 ± 0.1* | 92 ± 3 | 8.4 ± 0.1* |
| GLP-1-gly2 | 7.0 ± 0.2 | 45 ± 5 | 7.1 ± 0.1 | 7.7 ± 0.1* | 86 ± 3* | 7.8 ± 0.1 |
a
Mean ± SEM signaling parameter estimates from concentration response data shown in Figure 1, i.e., DERET assay (Figure 1E), n = 5, and high content microscopy assay using BG-S-S-649 (Figure 1I), n = 11. Signaling parameter estimates were determined from 3-parameter fitting. *p < 0.05 versus GLP-1, determined by one-way ANOVA with Dunnett’s test.