TABLE 3

Potencies of various selective OX1, OX2, and dual OX1/OX2 antagonists in the inhibition of [3H]almorexant binding to the membrane preparations from HEK293 cells transiently expressing hOX1 or hOX2

Ki and nH values for [3H]almorexant binding inhibition by various antagonists were calculated as described under Materials and Methods. Values are mean ± S.E., calculated from three independent experiments (each performed in duplicate).

[3H]Almorexant Competition Binding (37°C)
OX Antagonists hOX1 hOX2
KinHKinH
nM nM
Almorexant 4.7 ± 0.9 1.1 ± 0.1 0.9 ± 0.0 1.3 ± 0.0
Cp-1 25.7 ± 1.8 0.8 ± 0.1 0.7 ± 0.0 1.0 ± 0.0
Cp-2 3.3 ± 0.8 1.5 ± 0.1 2.4 ± 0.1 1.1 ± 0.0
Cp-3 8.4 ± 2.2 1.3 ± 0.1 5.1 ± 0.4 1.0 ± 0.0
SB-674042 1.9 ± 0.5 1.8 ± 0.2 133.5 ± 53.0 0.8 ± 0.0
SB-408124 32.7 ± 1.8 2.1 ± 0.7 1850 ± 670.0 1.8 ± 0.5
SB-334867 41.6 ± 2.8 1.9 ± 0.1 6300.0 ± 2000.0 0.8 ± 0.0
EMPA 4533 ± 1580 0.9 ± 0.1 1.2 ± 0.1 1.0 ± 0.0
Cp-4 782.0 ± 212.0 1.1 ± 0.0 3.86 ± 0.3 1.1 ± 0.1
Cp-5 >10,000 33.4 ± 2.3 0.8 ± 0.0