Table 1.

Kinase inhibitory activity of paroxetine analogs

R	Compound	GRK2 IC50 (μM)a	GRK1 IC50 (μM)a	GRK5 IC50 (μM)a	PKA IC50 (μM)a	ROCK1*
H	Paroxetine	1.38±1.00	> 100	> 100	> 100	10%
	1	0.02±0.001	9.1±3.2	2.2±0.9	ND	ND
	2	0.03±0.006	52.1±26.3	9.2±3.0	ND	ND
	3	0.77±0.5	> 100	> 100	30±19	65%
	14aa	2.1±0.72	> 100	> 100	> 100	11%
	14ab	0.77±0.17	> 100	84.3±35.8	> 100	17%
	14ac	2.68±2.11	> 100	> 100	> 100	22%
	14ad	1.53±0.49	> 100	37.2±28.9	> 100	34%
	14ae	2.03±0.33	> 100	10.2±1.8	> 100	0%
	14af	12.4±7.7	> 100	75.7±39.9	> 100	5%
	14ag	2.17±0.79	24.5±19.6	42.3±16.3	> 100	0%
	14ah	1.76±1.43	25.8±16.1	33.2±2.48	> 100	0%
	14ai	2.04±1.02	32.0±14.0	38.4±16.1	>100	13%
	14aj	37.7±9.14	> 100	> 100	> 100	1%
	14ba	2.37±2.27	> 100	> 100	25.8±25	18%
	14ak	0.61±0.12	> 100	17.1±5.9	> 100	6%
	14al	1.52±0.78	> 100	76.3±15.3	> 100	6%
	14am	2.04±0.74	> 100	> 100	> 100	8%
	14an	3.28±1.8	> 100	> 100	> 100	15%
	14ao	3.02±0.99	> 100	> 100	> 100	18%
	14ap	3.24±1.0	> 100	> 100	> 100	21%
	14bb	6.01±2.08	60.0±2.07	> 100	48.2±35	0%
	14bc	5.9±3.2	> 100	> 100	> 100	0%
	14aq	0.75±0.32	> 100	14.8±3.2	> 100	18%
	14ar	0.6±0.21	> 100	> 100	> 100	11%
	14as	0.03±0.001	87.3±27.9	7.09±0.73	> 100	9%
	14at	0.77±0.20	> 100	> 100	> 100	18%
	14au	0.03±0.02	86.5±7.0	4.0±0.52	> 100	12%
	14av	1.25±0.30	> 100	> 100	> 100	17%
	14aw	2.11±0.52	> 100	> 100	> 100	14%
	14ax	0.39±0.11	> 100	> 100	> 100	19%
	14ay	16.7±5.4	> 100	> 100	> 100	13%
	14bd	0.63±0.33	> 100	> 100	> 100	27%

^aAll IC₅₀ measurements are an average of three separate experiments run in duplicate. Errors shown represent error of the mean.

^*Percent inhibition at 10 μM inhibitor concentration. ND, not determined.