TABLE 1

Summary of in vitro properties of AAK1 inhibitors

AssayLP-935509LP-922761BMT-090605BMT-124110
Average IC50 ± S.E.M. (n), nM
AAK1 enzyme3.3 ± 0.7 (8)4.8 (2)0.6 ± 0.1 (9)0.9 ± 0.2 (7)
AAK1 binding3.3 ± 1.5 (4)3.6 (2)0.4 ± 0.1 (4)1.0 (1)
AAK1 cell assay2.8 ± 0.4 (26)7.6 ± 0.7 (58)0.6 ± 0.4 (4)3.2 ± 1.4 (2)
BIKE enzyme14 (1)24 (1)45 (1)17 (1)
GAK enzyme320 ± 40 (2)NA60 (1)99 (1)
μ Opioid receptor binding>30,000 (1)15,000 (1)>30,000 (1)>30,000 (1)
κ Opioid receptor binding>30,000 (1)>30,000 (1)29,000 (1)>30,000 (1)
Adrenergic α2A receptor binding> 30,000 (1)> 30,000 (1)> 30,000 (1)>30,000 (1)
Adrenergic α2C receptor binding>30,000 (1)>30,000 (1)>30,000 (1)15,000 (1)
Adrenergic α2A functional>1,000 (4)NA>10,000 (4)NA
Adrenergic α2C functional>1,000 (3)NA>10,000 (3)NA
GABAa α1 receptor modulator12,000 (3)>30,000 (1)>30,000 (1)>30,000 (1)
GABAa α2 receptor modulator12,000 (3)NANANA