TABLE 3
Structure and activity of selected benzoylpiperazines
Data show FUS1-HIS3 activation of GPR55-expressing yeast by test compound (10 μM) relative to a standard agonist (Activity in Screen) and confirmatory of concentration-response curves performed with yeast, HEK293aeq, or HEKMSRII cells expressing human or rat GPR55 (hGPR55 or rGPR55) or controls (cannabinoid CB1 and adrenergic α1A; all human). GlyT1 inhibition in [3H]glycine-binding SPA assay is also shown. Data are the mean (±S.D.) of duplicate or greater determinations.
| Compound | Activity in Screena | Concentration Response Curves | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Yeast [pEC50 (IA)] | BIND [pEC50] | Aequorin [pEC50 (IA)] | SPA pIC50 | |||||||
 | hGPR55 | rGPR55 | CB1 | hGPR55 | hGPR55 | α1A | GlyT1 | |||
| X | Y | |||||||||
| GSK494581Ab | 4-F-Ph |  | 123 ± 7 | 6.5 (1.1) | <4.5 | <4.5 | 6.5 | 6.8 (1.1) | NT | 7.7 |
| GSK598945Ab | 4-F-Ph |  | 64 ± 6 | 5.4 (0.8) | <4.5 | <4.5 | 5.5 | 5.5 (1.3) | <4.4 | 8.2 |
| GSK553224Ab | 4-F-Ph |  | 11 ± 1 | 5 (1.0) | <4.5 | <4.5 | 5.7 | 4.9 (0.8) | <4.4 | 7.9 |
| GSK522373Ab | 4-F-Ph |  | 98 ± 3 | 6.2 (1.0) | <4.5 | <4.5 | 5.7 | 5.8 (1.3) | <4.4 | 7.1 |
| GSK452334Ab | Ph |  | 30 ± 1 | 5.2 (0.4) | NT | <4.5 | 6.1 | 5.7 (0.9) | <4.4 | 8.1 |
| GSK319199Ac |  |  | 68 ± 4 | 5.5 (0.8) | NT | <4.5 | 5.7 | 5.1 (0.4) | <4.4 | 7.2 |
| GSK575594Ab | 4-F-Ph |  | NT | 6.8 (0.9) | <4.5 | <4.5 | NT | NT | NT | 5.0 |
IA, intrinsic activity; NT, not tested.
↵a Percent effect ± S.D.;