Supporting Information; Table 1
Structures and pharmacological profiles of key EP2 and EP4 receptor antagonists
utilised in these studies
Names
Structure
PF-04418948
MeO
Pharmacological profile
a
O
OH
O
N
Functional EP2 Ki = 7.6 nM (95% C.I., 5.6,
10.4 nM; n=22)
a
Functional EP1, EP3, EP4, DP1 Ki >10 M
a
Functional EP2 Ki = 0.63 nM (95% C.I., 0.19,
O
F
O
PF-04852946
OH
2.16; n=7)
N
O
O
a
Functional EP4 Ki = 16.3 M (95% C.I., 12,
22.3 M; n=5)
OMe
N
a
Functional DP1 Ki = 1.2 M (95% C.I., 1.1,
1.3 M; n=6)
O
CJ-042794
b
Cl
EP2 Ki = 768 nM (n=2)
N
OH
O
O
b
EP4 Ki = 2.94 nM (95% C.I., 0.78, 6.67 nM;
n=3); Functional cEP4 IC50 = 40.2 nM (95%
C.I., 31, 52.1 nM; n=4)
F
EP1 Ki = >17.6 M (n=2)
b
EP3 Ki = >14.8 M (n=2)
b
a
Data generated using methods or as reported by af Forselles and colleagues [1]
b
c
Binding data generated as reported by Murase and co-workers [2]
Functional data as reported by Murase and co-workers [2]
1.
af Forselles K, Root J, Clarke T, Davey D, Aughton K, Dack K, Pullen N.
In vitro and in vivo characterisation of PF-04418948, a novel, potent and
selective prostaglandin E2 receptor-2 (EP2) antagonist. Br J Pharmacol
2011; 164:1847-56.
2.
Murase A, Taniguchi Y, Tonai-Kachi H, Nakao K, Takada J. In vitro
pharmacological characterization of CJ-042794, a novel, potent, and
selective prostaglandin EP(4) receptor antagonist. Life Sci 2008; 82:22632.
2
Supporting Information; Figure 1
A
80
control
% inhibition
60
+ PF-04852946
40
20
0
-20
-8
-7
-6
-5
-4
-5
-4
log [PGE2] (M)
B
80
control
% inhibition
60
+ PF-04852946
40
20
0
-20
-8
-7
-6
log [misoprostol] (M)
Figure 1 Effect of the EP2 receptor antagonist, PF-04852946, on (A) PGE2 and (B)
misoprostol. Mast cells were incubated (50 min) without or with PF-04852946 (30
nM) and then without or with PGE2 or misoprostol for 10 min before challenge with
anti-IgE (2 µg/mL) for 25 min. Values are expressed as the % inhibition of control
histamine release which were 23 ± 4 and 25 ± 5% for (A) and 22 ± 3 and 23 ± 3% for
(B). Values are means ± SEM for 5 and 4 experiments for (A) and (B), respectively.