Table 6.
EP2 Potency, selectivity index (S.I), and cytotoxicity (CC50) of selected novel EP2 antagonistsa
| Entry | EP2 KB (nM) | DP1 KB (μM) | S.I. (DP1/EP2) | EP4 KB (μM) | S.I (EP4/EP2) | IP KB (μM) | S.I (IP/EP2) | CC50 (μM) |
|---|---|---|---|---|---|---|---|---|
| 8a | 23.2 | 1.0 | 42 | ND | ND | ND | ND | ND |
| 8b | 9.5 | 0.9 | 95 | ND | ND | ND | ND | ND |
| 8c | 10 | 3.0 | 300 | 22.8 | 2280 | 3.47 | 350 | 21 |
| 8e | 48.4 | 0.8 | 16 | ND | ND | ND | ND | ND |
| 8g | 2.9 | 1.2 | 410 | 3.91 | 1350 | 0.73 | 25 | >50 |
| 11a | 48.6 | 1.7 | 35 | ND | ND | ND | ND | ND |
| 11b | 33.6 | 0.5 | 15 | ND | ND | ND | ND | ND |
| 14a | 29.6 | 6.6 | 300 | 15.3 | 517 | 21.5 | 730 | >50 |
| 20a | 10.7 | >10 | >900 | 6.7 | 630 | >10 | >900 | >50 |
| 20c | 6.4 | 3.2 | 500 | >10 | >1500 | >10 | >1500 | >50 |
| 20e | 6.1 | 2.25 | 360 | >10 | >1500 | >10 | >1500 | >50 |
| 20h | 7.8 | >10 | >1280 | 6.7 | 860 | >10 | >1280 | >50 |
| 20o | 9.7 | 7.32 | 750 | 5.3 | 550 | >10 | >1000 | >50 |
| 20q | 8.3 | 1.77 | 213 | >10 | >1200 | >10 | >1200 | >50 |
| 24a | 13.0 | 9.0 | 692 | 3.1 | 240 | >10 | 770 | >50 |
| 24b | 28.3 | 8.2 | 290 | >10 | >350 | >10 | >350 | >50 |
| 24c | 20.0 | 8.2 | 410 | 3.8 | 193 | >10 | >500 | ND |
a
EP2 KB values are from average of 2 independent experiments run duplicate, except for 20o. EP4, DP1 and IP KB values are from 2 independent experiments run in duplicate. KB values for EP2 are in the nanomolar scale, whereas KB values for other receptors are shown in micromolar scale. CC50 (concentration required to kill 50% C6glioma cells) values are from 1–2 experiments run in triplicate using internal standard doxorubucin, which showed CC50 = 0.9 μM.