Table 2. Potency and Selectivity of Inhibitors among the GRKs and PKA.
| GRK1 |
GRK2 |
GRK5 |
PKA | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| log IC50 | foldb | log IC50 | fold | log IC50 | fold | log IC50 | Sseld | |||
| paroxetinea | –3.4 | –5.9 | –3.9 | >−3.3c | 0.085 | GRK2 | ||||
| indazole class | GSK180736A | >−3 | NA | –6.6 | 5.0 | –4.0 | 1.3 | >−3.3 | 0.022 | GRK2 |
| GSK299115A | >−3 | NA | –5.5 | 0.40 | –4.1 | 1.6 | –4.2 | 0.360 | GRK2 | |
| GSK466317A | –3.0 | 0 | –4.5 | 0.040 | –4.4 | 3.2 | –4.9 | 1.001 | NON | |
| GSK317354A | >−3 | NA | –5.6 | 0.50 | –3.2 | 0.20 | –3.7 | 0.109 | GRK2 | |
| GSK270822A | –3.1 | 1 | –4.9 | 0.10 | –4.2 | 2.0 | –4.3 | 0.883 | NON | |
| pyrrolopyrimidine class | GSK2163632A | –6.9 | 3162 | –4.7 | 0.063 | –5.5 | 40 | >−3.3 | 0.199 | GRK1 |
| GSK2110236A | –6.2 | 631 | –4.7 | 0.063 | –5.5 | 40 | >−3.3 | 0.561 | NON | |
| GSK2220400A | –5.0 | 40 | –3.7 | 0.0063 | –5.2 | 20 | >−3.3 | 0.770 | NON | |
| GSK1713088A | –4.9 | 32 | –5.2 | 0.20 | –5.5 | 40 | >−3.3 | 0.968 | NON | |
| GSK1326255A | –3.3 | 1 | –5.1 | 0.16 | –5.6 | 50 | >−3.3 | 0.586 | NON | |
| other | GW693881A | >−3 | NA | –3.7 | 0.0063 | –4 | 1.3 | >−3.3 | 1.005 | NON |
| GW416981X | –3.0 | 0 | >−3 | NA | –4.6 | 5.0 | >−3.3 | 0.330 | GRK5 | |
| GSK1007102B | –4.2 | 6 | –6.0 | 1.3 | –5.5 | 40 | –6.3 | 0.917 | NON | |
| GW806742X | >−3 | NA | >−3 | NA | >-3 | NA | >−3.3 | 1.386 | NON | |
a
Paroxetine was not in the primary screen but is included as a benchmark to calculate fold changes in potency.
b
Increase in potency relative to paroxetine.
c
Compound solubility limited the assay to effectively measure only IC50 values lower than 1 mM (GRK assays) or 0.5 mM (PKA assays); thus, potencies weaker than this are reported as log IC50 ≥ −3 or ≥ −3.3, respectively.
d
Selectivity is determined by having a Ssel of <0.5; thus, all values ≥0.5 are considered to be nonselective.