TABLE 2.
EC50 and Emax values for CB2 ligands in the cyclase and arrestin assays
The EC50 values presented with 95% confidence intervals, while the Emax data are presented as mean ± S.E.M. and P values (*P < 0.05; **P < 0.01, ***P < 0.001). The P values were obtained use the Student’s t test and by comparing the efficacy of the test compound at 1 µM with the effect of 1 µM CP55940. For antagonists, the comparisons were to basal signaling. The *P and **P values represent compounds meeting >20% activation or inhibition thresholds (compared with CP55940); the ***P values represent compounds that failed to meet the 20% activation or inhibition thresholds (compared with CP55940).
| Compound |
Cyclase Assay |
Arrestin Recruitment Assay |
||||||
|---|---|---|---|---|---|---|---|---|
| EC50 |
95% CI |
Emaxa |
P value |
EC50 |
95% CI |
Emax |
P value |
|
| nM | nM | % | nM | |||||
| CP55940 | 3 | 1.1–8.5 | 57 ± 0.5 | NA | 3.2 | 0.2–5.5 | 100 | NA |
| THC | 7.3 | 2.3–20.4 | 52 ± 1.2 | * | NA | NA | 3 ± 1.3 | *** |
| L759633 | NA | NA | NA | NA | NA | NA | 10 ± 1.5 | *** |
| L759656 | NA | NA | NA | NA | NA | NA | 11 ± 1.1 | *** |
| JWH133 | 20 | 15.5–28.1 | 61 ± 1.1 | * | NA | NA | 18 ± 2.1 | *** |
| KM233 | 1.6 | 0.2–7.7 | 50 ± 1.3 | ** | NA | NA | 17 ± 3.4 | *** |
| HU308 | 30 | 27.6–35.1 | 60 ± 3.4 | NS | NA | NA | 3 ± 1.6 | *** |
| WIN55212-2 | 16 | 10.5–21.7 | 40 ± 1.2 | ** | 7.2 | 3.4–11.0 | 30 ± 1.2 | * |
| AM1241 | 20 | 18.1–22.5 | 27 ± 5.2 | * | NA | NA | 17 ± 1.9 | *** |
| STS135 | 52 | 40.9–65.11 | 31 ± 2.3 | * | 1.5 | 1–3.9 | 62 ± 1.1 | * |
| JWH015 | 30 | 24.4–38.1 | 23 ± 0.72 | * | 160 | 101–225 | 28 ± 1.5 | ** |
| GW405833 | NA | NA | 0 | *** | NA | NA | 4 ± 2.6 | *** |
| UR144 | NA | NA | 12 ± 0.7 | 95 | 78.2–135 | 70 ± 1.2 | ** | |
| MAM2201 | 7 | 1.1–11.5 | 26 ± 2.1 | * | NA | NA | 12 ± 3.4 | *** |
| AM2232 | 22 | 17.3–24.3 | 24 ± 1.3 | * | NA | NA | 15 ± 2.7 | *** |
| AM2233 | NA | NA | 7 ± 1.6 | *** | NA | NA | 10 ± 1.5 | *** |
| AM1248 | 15 | 12.3–17.3 | 24 ± 3.1 | * | 71 | 62.1–99 | 52 ± 2.3 | * |
| A836339 | 43 | 39.2-46 | 54 ± 1.1 | NS | 0.7 | 0.04–2.4 | 100 (NS) | NS |
| GP1a | 14 | 10.1–25.2 | 51 ± 7.6 | NS | 17 | 9.1–27.3 | 38 ± 1.2 | * |
| AM1710 | 11 | 5.5–15.6 | 48 ± 4.3 | NS | 4 | 1.6–7.1 | 91 ± 3.6 | NS |
| SER601 | 40 | 19.2–76.1 | 25 ± 1.1 | ** | NA | NA | NA | NA |
| 4Q3C | NA | NA | NA | NA | NA | NA | NA | NA |
| GW833972A | 28 | 20–56.1 | 22 ± 7.5 | * | 90 | 56.1–135 | 88 ± 2.5 | ** |
| 2AG | 4.1 | 0.4–7.8 | 39 ± 0.7 | * | NA | NA | NA | NA |
| Methanandamide | 20 | 17.9–25.3 | 55 ± 0.5 | * | NA | NA | NA | NA |
| 4 Methylhonokiol | NA | NA | NA | NA | 51 | 42.1–62 | 55 ± 4.6 | ** |
| β Caryophyllene | 30 | 22.1–36.6 | 5 ± 1.1 | *** | NA | NA | NA | NA |
| AM630 | 25 | 21.6–29.3 | 19 ± 2.4b | ** | 9 | 3.8–14.4 | 43 ± 4.2 | ** |
| JTE907 | 22 | 14.1–24.5 | 8 ± 0.8b | ** | 0.1 | 0.01–3.6 | 47 ± 1.5 | ** |
| SR144528 | NA | NA | 11 ± 0.7b | ** | 15 | 11–18.3 | 43 ± 3.1c | ** |
AM1241, (2-iodo-5-nitrophenyl)-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone; AM1248, 1-[(N-methylpiperidin-2-yl)methyl]-3-(adamant-1-oyl)indole; AM2232, (1-(4-cyanobutyl)-3-(naphthalen-1-oyl)indole); A836339, N-[3-(2-methoxyethyl)-4,5-dimethyl-1,3-thiazol-2-ylidene]-2,2,3,3-tetramethylcyclopropane-1-carboxamide; CI, confidence interval; Emax, maximal inhibition of forskolin-stimulated cAMP production; GP1a, N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-1,4-dihydro-6-methylindeno[1,2-c]pyrazole-3-carboxamide; GW833972A, 2-[(3-chlorophenyl)amino]-N-(4-pyridinylmethyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide hydrochloride; HU308, 4-[4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-methanol; JTE907, N-(1,3-benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinolinecarboxamide; JWH015, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone; JWH133, (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran; KM233, (−)-(6aR,7,10,10aR)-tetrahydro-6,6,9-trimethyl-3-(1-methyl-1-phenylethyl)-6H-dibenzo[b,d]pyran-1-ol; L759633, (6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene; L759656, (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,8,9,10,10a-hexahydro-1-methoxy-6,6-dimethyl-9-methylene-6H-dibenzo[b,d]pyran; MAM2201, [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)-methanone; NA, not applicable/cannot be determined (inhibition or activation <20% threshold); NS, non statistically significant difference; SER601, N-(Adamant-1-yl)-6-isopropyl-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide THC, tetrahydrocannabinol; 4Q3C, 1,4-dihydro-8-methoxy-4-oxo-1-pentyl-N-tricyclo[3.3.1.13,7]dec-1-yl-3-quinolinecarboxamide; WIN55212-2, [(3R)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, monomethanesulfonate.
Percentage of inhibition of forskolin-stimulated cAMP production.
Above basal.
Below basal.