Table 5.
Key pharmacological features of recently discovered potent and selective prostanoid EP4 receptor antagonists
| |
Binding |
Functional |
|||||
|---|---|---|---|---|---|---|---|
| Human pKi | Rodent pKi | Human EP4 pKb | Human selectivity | Animal EP4 pKb | Animal EP4 pIC50 | Animal selectivity | |
| GW627368X |
EP4 7.0 |
— |
7.9 |
EP1 pA2 6.0 |
9.2 (porcine) |
— |
TP <5.0 rabbit and guinea-pig |
| |
TP 6.8 |
|
Competitive |
DP not tested |
⩾8.7 (rabbit)a |
|
|
| |
Other <5.3 |
|
Inverse agonist? |
TP pIC50 5.0–6.0 |
|
|
|
| |
|
|
|
Other <5.6 |
|
|
|
| EP4Ab |
EP4 7.6 |
EP4 7.5 (rat) |
8.4c |
— |
— |
7.0 (rat) |
— |
| |
EP3 5.7 |
|
Competitive |
|
|
|
|
| |
TP 6.2 |
|
|
|
|
|
|
| |
Other <5.3 |
|
|
|
|
|
|
| ONO-AE2-227d |
— |
EP4 8.5 (murine) |
— |
— |
— |
8.0 (murine) |
— |
| |
|
EP3 7.7 (murine) |
|
|
|
|
|
| |
|
Other <5.5 (murine) |
|
|
|
|
|
| Compound 8e |
EP4 9.5 |
EP4 9.1 (rat) |
— |
— |
— |
>8.0 (murine) |
— |
| |
Other <5.5 |
|
|
|
|
|
|
| Compound 11e |
EP4 9.0 |
EP4 8.3 (rat) |
— |
— |
— |
7.0–8.0 (murine) |
— |
| Other <5.0 | |||||||
Systematic compound names are given in Abbreviations.
a
Data taken from Jones & Chan (2005).
b
Data taken from Machwate et al. (2001).
c
Data taken from Davis et al. (2004).
d
Data taken from Mutoh et al. (2002).
e
Data taken from Hattori et al. (2005).