Binding affinity and potency and efficacy for stimulation of GTPγ[35S] binding at hCB1 and hCB2 receptors
| Compound | CB1 Kia | GTPγ[35S] Bindingb | CB2 Kia | GTPγ[35S] Bindingb | ||
|---|---|---|---|---|---|---|
| CB1 EC50c | CB1 Emaxd | CB2 EC50c | CB2 Emaxd | |||
| CP55,940 | 0.90 (0.76–1.1) | 14.3 (5.38–38.2) | 211 (197–225) | 1.13 (0.91–1.41) | 3.17 (1.09–9.18) | 163 (152–174) |
| 11 | 15 | 15 | 7 | 13 | 13 | |
| XLR-11 | 21.2 (15.0–29.8) | 88.5 (16.3–481) | 205 (177–233) | 1.45 (0.94–2.23) | 39.0 (0.69–2220) | 135 (116–154) |
| 3 | 5 | 5 | 3 | 5 | 5 | |
| XLR-11 degradant | 2.84 (2.14–3.75) | 90.2 (52.0–157) | 364 (342–386)) | 1.03 (0.72–1.50) | 3.32 (0.17–64.4) | 162 (147–178) |
| 4 | 8 | 8 | 3 | 6 | 6 | |
| UR-144 | 25.9 (18.5–36.2) | 93.0 (13.3–651) | 193 (164–221) | 2.72 (1.71–4.34) | 97.4 (1.57–6027) | 140 (122–158) |
| 3 | 5 | 5 | 3 | 5 | 5 | |
| UR-144 degradant | 5.62 (4.13–7.65) | 140 (82.3–239) | 381 (358–405) | 1.81 (1.20–2.72) | 3.65 (0.72–18.5) | 169 (156–183) |
| 4 | 8 | 8 | 3 | 6 | 6 | |
| A-834735 | 18.3 (11.6–29.0) | 1088 (428–2770) | 417 (351–483) | 1.06 (0.77–1.46) | 3.28 (0.21–50.9) | 163 (142–183) |
| 3 | 4 | 4 | 3 | 4 | 4 | |
| A-834735 degradant | 2.30 (1.75–3.03) | 88.6 (54.1–145) | 395 (373–416) | 0.71 (0.49–1.05) | 1.50 (0.22–10.4) | 166 (154–177) |
| 4 | 8 | 8 | 3 | 6 | 6 | |
| PB-22 | 1.09 (0.81–1.47) | 30.9 (12.8–74.5) | 415.4 (373–458) | 5.61 (3.88–8.12) | >10 μM (NA) | NA |
| 3 | 2 | 2 | 3 | 2 | ||
| 3-carboxyindole metabolite of PB-22 | >10 μM (NA) | >10 μM (NA) | NA | >10 μM (NA) | >10 μM (NA) | NA |
| 4 | 8 | 3 | 8 | |||
| N-pentylindole | >10 μM (NA) | Not tested | Not tested | >10 μM (NA) | Not tested | Not tested |
| 2 | 3 | |||||
| 8-OH-quinoline | >10 μM (NA) | Not tested | Not tested | >10 μM (NA) | Not tested | Not tested |
| 3 | 3 | |||||
NA, not applicable.
↵a Values represent Ki values (± S.E.M.) in nM for [3H]CP55,940 displacement at specified (hCB1 or hCB2) receptor.
↵b For each measure in all columns, n is shown below the SEM.
↵c Values represent EC50 values (95% confidence interval) in nM for GTPγ[35S] binding at specified (hCB1 or hCB2) receptor.
↵d Values represent percentage GTPγ[35S]-specific binding with basal set at the global percentage shared (∼100%) determined at the specified (hCB1 or hCB2) receptor subtype.