Table 1.
Kinase inhibitory activity of new analogs of 12 and 13.
| ||||||
|---|---|---|---|---|---|---|
| Compound | R | GRK2 IC50 (μM) |
GRK1 IC50 (μM) |
GRK5 IC50 (μM) |
PKA IC50 (μM) |
ROCK IC50 (μM) |
| Paroxetine | – | 1.38±1.00 | >100 | >100 | >100 | 10%* |
| 1 | – | 0.02±0.001 | 9.0±3.2 | 2.2±0.92 | ND | 10%* |
| 2 | H | 0.77±0.5 | >100 | >100 | 30±19 | 0.10±0.09 |
| 10 | COOH | 20±10 | >100 | >100 | 78.1±72 | 0.19±0.14 |
| 12a | CONHMe | 4.3±0.7 | >100 | >100 | >100 | 0.56±0.68 |
| 12b | CONHBn | 0.69±0.3 | 71±2 | 4.7±1.9 | >100 | 0.069±0.044 |
| 12c |
|
0.20±0.1 | 11.9±2.3 | 0.80±0.0.1 | >100 | 0.021±0.13 |
| 12d |
|
0.22±0.2 | >100 | 5.0±1.2 | >100 | 0.11±0.084 |
| 12e |
|
0.060±0.03 | 16±6.4 | 2.3±2.7 | >100 | 0.057±0.044 |
| 12f |
|
0.42±0.05 | >100 | 3.8±0.9 | >100 | 0.097±0.076 |
| 12g |
|
0.46±0.3 | >100 | 8.1±4.7 | >100 | 0.050±0.011 |
| 12h |
|
0.15±0.07 | 3.9±1.0 | 0.38±0.06 | >100 | 0.011±0.013 |
| 12i |
|
0.28±0.1 | >100 | 6.2±3.8 | >100 | 0.023±0.022 |
| 12j |
|
4.8±1.9 | >100 | 40.0±14 | >100 | 0.084±0.009 |
| 12k |
|
0.28±0.06 | 0.10±0.05 | 1.8±0.54 | ND | 0.012±0.004 |
| 12l |
|
0.13±0.03 | >100 | >100 | >100 | 6.7±8.2 |
| 12m |
|
0.07±0.01 | >100 | 63±32 | >100 | 5.8±5.5 |
| 12n |
|
0.13±0.03 | >100 | >100 | >100 | 0%* |
| 12o |
|
1.2±0.7 | >100 | >100 | >100 | 22%* |
| 12p |
|
2.7±2.3 | >100 | >100 | >100 | 1.9±0.25 |
| 12q |
|
1.9±1.3 | >100 | 68±26 | >100 | 0.15±0.05 |
| 13a |
|
25±12 | >100 | 88±60 | >100 | 0.45±.28 |
| 13b |
|
>100 | >100 | >100 | >100 | 0.40±0.32 |
| 13c |
|
0.45±0.29 | >100 | >100 | >100 | 0.20±0.05 |
| 12r |
|
0.23±0.05 | >100 | 58±13 | >100 | 0.29±0.033 |
All IC50 measurements are an average of three separate experiments run in duplicate.
Errors shown represent standard error of the mean.
*
Percent inhibition at 10 μM inhibitor concentration.