TABLE 1

Kinase activity and half-life in mouse liver microsomes of indazole-paroxetine hybrids

CCG#	R¹	R²	GRK2 IC₅₀ (μM)^{^a}	GRK1 IC₅₀ (μM)^{^a}	GRK5 IC₅₀ (μM)^{^a}	PKA IC₅₀ (μM)^{^a}	ROCK1^{^b} (%)	MLM t_1/2 (min)
224061	H	H	0.066 (1.1)	6.4 (1.3)	1.3 (1.2)	3.1 (1.4)	100 ± 1.5	30
258002	H	F	0.13 (1.6)	3.6 (1.3)	0.81 (1.2)	3.4 (1.6)	48 ± 5.8	22
232406		H	0.36 (1.8)	>100	28.8 (1.7)	9.8 (1.2)	63 ± 6.2	8.3
258003		F	0.36 (1.7)	40 (1.1)	8.0 (1.2)	24 (1.9)	80 ± 8.4	13
257284		H	0.10 (1.2)	3.9 (1.5)	0.49 (1.1)	15 (1.3)	100 ± 5.7	2.7
258748		H	0.008 (1.3)	4.4 (1.3)	0.24 (1.2)	62 (1.6)	83 ± 2.4	8.1

↵^a All IC₅₀ measurements are reported as the geometric mean of three separate experiments run in duplicate. Error is expressed in parenthesis as the geometric S.D. factor (multiplied or divided by the mean).
↵^b Percent inhibition at an inhibitor concentration of 10 μM, error is expressed as the S.D.