Extended Data Table 3 |.
Potency table for drugs profiled in Extended Data Fig. 6
| Potency | ||||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Compounds | Gi1 EC50 nM (pEC50 ± SEM) |
Gi2 EC50 nM (pEC50 ± SEM) |
Gi3 EC50 nM (pEC50 ± SEM) |
G0a EC50 nM (pEC50 ± SEM) |
G0b EC50 nM (pEC50 ± SEM) |
Gz EC50 nM (pEC50 ± SEM) |
β-arrl EC50 nM (pEC50 ± SEM) |
β-arr2 EC50 nM (pEC50 ± SEM) |
| Opioid Peptides | ||||||||
| DAMGO | 18 (7.7 ± 0.1) | 5 (8.2±0.1) | 15 (7.8±0.1) | 5 (8.3±0.1) | 2.5 (8.6±0.1) | 5.6 (9.2±0.1) | 189 (6.7±0.1) | 171 (6.8±0.1) |
| Endomorphin-1 | 9.9 (8.0 ± 0.1) | 4.3 (8.4 ± 0.1) | 16 (7.8 ± 0.1) | 8.0 (8.1 ± 0.1) | 6.0 (8.2 ± 0.1) | 3.0 (8.5 ± 0.1) | 11 (7.9 ± 0.1) | 21 (7.7 ± 0.1) |
| Leu-Enkephalin | 39 (7.4 ± 0.1) | 5.1 (8.3 ± 0.2) | 47 (7.3 ± 0.1) | 8.6 (8.1 ± 0.1) | 6.7 (8.2 ± 0.1) | 1.8 (8.8 ± 0.1) | 98 (7.0 ± 0.2) | 90 (7.1 ± 0.2) |
| Met-Enkephalin | 54 (7.3 ± 0.1) | 10 (8.00 ± 0.3) | 79 (7.1 ± 0.1) | 12 (7.9 ± 0.1) | 8.6 (8.1 ± 0.1) | 5.3 (8.3 ± 0.1) | 39 (7.4 ± 0.2) | 193 (6.7 ± 0.2) |
| Beta-Enkephalin | 128 (6.9 ± 0.1) | 93 (7.0 ± 0.2) | 293 (6.5 ± 0.1) | 62 (7.2 ± 0.1) | 55 (7.3 ± 0.2) | 13 (7.9 ± 0.1) | 28 (7.6 ± 0.2) | 120 (6.9 ± 0.1) |
| Dynorphin 1-17 | 88 (7.1 ± 0.1) | 18 (7.7 ± 0.1) | 115 (6.7 ± 0.1) | 25 (7.6 ± 0.1) | 43 (7.4 ± 0.1) | 167 (7.8 ± 0.1) | nd | nd |
|
| ||||||||
| Biased Opiates | ||||||||
| PZM21 | 53 (7.3 ± 0.07) | 10 (8.0 ± 0.1) | 55 (7.3 ± 0.1) | 52 (7.3 ± 0.1) | 28 (7.6 ± 0.1) | 9.8 (8.0 ± 0.1) | 104 (7.0 ± 0.2) | 199 (6.7 ± 0.4) |
| 7-OH | 111 (6.9 ± 0.3) | 76 (7.1 ± 0.2) | nd | 39 (7.4 ± 0.2) | 55 (7.3 ± 0.2) | 8.6 (8.1 ± 0.1) | nd | nd |
| TRV130 | 51 (7.3 ± 0.1) | 5.9 (8.2 ± 0.2) | 26 (7.6 ± 0.2) | 12 (7.9 ± 0.2) | 18 (7.7 ± 0.1) | 6.4 (8.2 ± 0.1) | nd | 73 (7.1 ± 0.4) |
|
| ||||||||
| Partial agonists | ||||||||
| Pentazocine | 10 (8.0 ± 0.1) | 4.3 (8.4 ± 0.1) | 8.6 (8.1 ± 0.1) | 5.1 (8.3 ± 0.1) | 3.3 (8.5 ± 0.1) | 1.0 (9.0 ± 0.1) | nd | nd |
| Buprenorphine | 2.1 (8.6 ± 0.2) | 0.7 (9.1 ± 0.2) | 1.0 (9.0 ± 0.3) | 1.8 (8.7 ± 0.2) | 2.0 (8.9 ± 0.3) | 0.4 (9.3 ± 1.6) | nd | nd |
|
| ||||||||
| Prototypic agonists | ||||||||
| Oxycodone | 486 (6.3 ± 0.1) | 278 (6.6 ± 0.2) | 565 (6.3 ± 0.1) | 286 (6.5 ± 0.2) | 146 (6.8 ± 0.1) | 39 (7.4 ± 0.2) | 5300 (5.3 ±0.2) | 2061 (5.7 ± 0.1) |
| Carfentanil | 0.30 (9.5 ± 0.1) | 0.21 (9.6 ± 0.1) | 0.43 (9.4 ± 0.1) | 0.21 (9.7 ± 0.1) | 0.22 (9.8 ± 0.1) | 0.14 (10.2 ± 0.1) | 0.20 (9.7 ±0.2) | 0.32 (9.5 ± 0.2) |
| Fentanyl | 12.7 (7.9 ± 0.1) | 3.4 (8.4 ± 0.2) | 19.4 (7.7 ± 0.2) | 6.8 (8.2 ± 0.1) | 4.9 (8.3 ± 0.1) | 0.9 (9.0 ± 0.1) | 10.5 (8.0 ± 0.1) | 7.8 (8.1 ± O.q) |
| Morphine | 11.9 (8.0 ± 0.1) | 10.4 (8.0 ± 0.2) | 7.2 (8.1 ± 0.2) | 6.9 (8.2 ± 0.1) | 5.5 (8.3 ± 0.1) | 2.4 (8.6 ± 0.1) | 205 (6.7 ± 0.1) | 118 (6.9 ± 0.2) |
|
| ||||||||
| Bitopics | ||||||||
| C3-guano | 1234 (5.9 ± 0.2) | 562 (6.2 ± 0.2) | 1811 (5.7 ± 0.2) | 505 (6.3 ± 0.2) | 338 (6.5 ± 0.1) | 305 (6.5 ± 0.2) | n.d. | 23571(4.6 ± 0.5) |
| C5-guano | 453 (7.3 ± 0.1) | 79 (7.1 ± 0.1) | 350 (6.5 ± 0.2) | 23 (7.6 ± 0.1) | 24 (7.6 ± 0.2) | 8.8 (8.0 ± 0.1) | 1210 (5.9 ± 0.2) | 1760(5.7 ± 0.3) |
| C6-guano | 132 (6.9 ± 0.2) | 58 (7.2 ± 0.2) | 33 (7.5 ± 0.3) | 54 (57.3± 0.3) | 72 (7.1 ± 0.2) | 25 (7.6 ± 0.3) | n.d. | 5191(5.3±0.6) |
| C7-guano | 531 (6.3 ± 0.2) | 450 (6.3 ± 0.2) | 833 (6.1 ± 0.4) | 81 (7.1 ± 0.2) | 63 (7.2 ± 0.2) | 161 (6.8 ± 0.1) | n.d. | n.d. |
| C9-guano | 93.1 (7.0 ± 0.1) | 60 (7.2 ± 0.2) | 181 (6.7 ± 0.1) | 27 (7.6 ± 0.1) | 43 (7.6 ± 0.1) | 27 (7.6 ± 0.1) | 3215 (5.5 ± 0.2) | 4089 (5.4 ± 0.2) |
| C11-guano | 4745 (5.3 ± 0.1) | 1311 (5.9 ± 0.3) | 1065 (6.0 ± 0.3) | 1242 (5.9 ± 0.1) | 2038 (5.7 ± 0.1) | 861 (6.1 ± 0.1) | n.d. | 30885 (4.5 ± 0.2) |
Potency [EC50 nM (pEC50 ± SEM)] are reported as estimates from simultaneous curve fitting of all biological replicates and include standard error.