Table 1 Signaling parameters for the KOR agonists in the cell-based functional assays.

Data are presented as means ± SEM from n ≥ 3 independent experiments performed in duplicate to quadruplicate. Emax values were normalized calculation to the maximum stimulation by U69,593. Ca2+ accumulation, intracellular calcium mobilization assay; K+ accumulation, GIRK channel activation assay.

Compound[35S]GTPγS binding
EC50 (nM)Emax (%)LogRΔLogR
U69,59366 ± 131007.26 ± 0.090
1.196 ± 1095 ± 17.00 ± 0.05−0.29 ± 0.07
2.1155 ± 3094 ± 26.80 ± 0.07−0.44 ± 0.06
βarr2 recruitment (EFC)
EC50 (nM)Emax (%)LogRΔLogR
U69,593112 ± 111007.00 ± 0.060
1.13338 ± 40588 ± 65.44 ± 0.04−1.56 ± 0.09
2.12447 ± 27682 ± 45.59 ± 0.06−1.42 ± 0.09
Forskolin-stimulated cAMP accumulation
EC50 (nM)Emax (%)LogRΔLogR
U69,59312 ± 21008.02 ± 0.090
1.1309 ± 6594 ± 56.49 ± 0.12−1.64 ± 0.13
2.1303 ± 4698 ± 56.55 ± 0.04−1.33 ± 0.09
Ca2+ accumulation
EC50 (nM)Emax (%)LogRΔLogR
U69,59319 ± 51007.79 ± 0.120
1.11064 ± 18697 ± 95.96 ± 0.14−1.91 ± 0.16
2.11594 ± 49198 ± 85.97 ± 0.15−1.82 ± 0.19
K+ accumulation
EC50 (nM)Emax (%)LogRΔLogR
U69,5938 ± 21008.29 ± 0.180
1.121 ± 8108 ± 88.03 ± 0.27−0.23 ± 0.03
2.122 ± 6105 ± 97.85 ± 0.13−0.41 ± 0.18