Table 3.
Kinase inhibitory activity of indole-3-carbonitriles 6, 13 and 14 against DYRK1A and closely related kinases of the CMGC group a.
| Compound | IC50 [µM]/Residual Activity at 10 µM [%] | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| DYRK 1A |
DYRK 1B |
DYRK2 | DYRK3 | CLK1 | CLK2 | CLK3 | CLK4 | GSK3 | |
| 6a | 3.30 | >10 | >10 | >10 | 3.33 | >10 | >10 | >10 | >10 |
| 6b | 1.10 | 5.9 | >10 | >10 | 2.9 | >10 | >10 | 4 | >10 |
| 6c | 0.410 | 1.8 | 8 | >10 | 1.9 | 8 | >10 | 1.8 | >10 |
| 6d | 0.4 | 6 | - | - | 0.800 | >10 | - | 2 | - |
| 6e | 35% | 74% | 75% | 105% | 56% | 75% | 124% | 43% | n.t. |
| 6f | 0.040 | >10 | >10 | >10 | 0.070 | >10 | >10 | 0.120 | >10 |
| 6g | 0.025 | 0.120 | >10 | >10 | 0.067 | 0.433 | >10 | 0.033 | n.t. |
| 6h | 0.010 | 0.570 | >10 | >10 | 0.080 | 2 | >10 | 0.050 | >10 |
| 6i | 60% | n.t. | n.t. | n.t. | 68% | n.t. | n.t. | n.t. | 112% |
| 6j | 60% | n.t. | n.t. | n.t. | 47% | n.t. | n.t. | n.t. | 118% |
| 6k | 0.690 | 1.3 | >10 | >10 | 0.533 | 1.3 | >10 | 0.533 | n.t. |
| 6l | 3.9 | >10 | >10 | >10 | 4.9 | >10 | >10 | 4 | n.t. |
| 6m | 42% | 79% | 116% | 101% | 55% | 92% | 130% | 36% | n.t. |
| 6n | 0.233 | >10 | >10 | >10 | 0.333 | >10 | >10 | 0.220 | n.t. |
| 6o | 0.210 | 0.633 | >10 | >10 | 0.633 | 3.3 | >10 | 0.290 | n.t. |
| 6p | 0.08 | 0.3 | - | - | 0.200 | >10 | - | >10 | n.t. |
| 6q | 0.28 | 0.53 | >10 | >10 | 0.1 | 0.7 | >10 | 0.1 | 1.3 |
| 6r | 0.14 | 0.5 | 8 | >10 | 0.110 | 1 | - | 0.1 | - |
| 6s | 0.07 | 0.6 | - | - | 0.12 | 1 | - | 0.1 | >10 |
| 13a | 97% | 78% | 144% | 95% | 102% | 95% | 127% | 84% | n.t. |
| 13b | 81% | n.t. | n.t. | n.t. | 53% | n.t. | n.t. | n.t. | 114% |
| 13c | 32% | 47% | 117% | 95% | 56% | 70% | 97% | 30% | n.t. |
| 13d | 1.9 | >10 | >10 | >10 | 3.33 | >10 | >10 | >10 | >10 |
| 13e | 2.3 | 10 | - | - | >10 | - | - | 1 | - |
| 13f | 0.65 | 2.1 | - | - | 0.6 | >10 | - | 1 | - |
| 14 | 2 | 4.2 | - | - | 2 | 10 | - | 2 | 2 |
a The activity is indicated as IC50 (µM) or as residual activity (%) at 10 µM compared to controls. -: less than 20% inhibition at 10 µM, IC50 was not determined; n.t.: not tested.