Table 1.
IC50 valuesa (nM) for pyrimidines having a guanidyl core
| ||||||||
|---|---|---|---|---|---|---|---|---|
| Compound | R1 | R2 | Clk1 | Clk2 | Clk3 | Clk4a | Dyrk1Aa | Dyrk1B |
| 10 |
|
|
277 | 1092 | -- | 319 (290) | 558 (2070) | 871 |
| 11 |
|
|
76 | 409 | -- | 92 (210) | 203 (1160) | 411 |
| 12 |
|
|
>10,000 | >10,000 | -- | 6806 (5820) | 6361 (7330) | 6782 |
| 13 |
|
|
5459 | >10,000 | -- | 3858 (3680) | 4654 (5820) | >10,000 |
| 14 |
|
|
(50) | (260) | ||||
| 15 |
|
|
8 | 20 | 3634 | 14 (40) | 26 (160) | 38 |
| 16 |
|
|
24 | 30 | 3232 | 18 (80) | 79 (820) | 112 |
| 17 |
|
|
2 | 23 | >10,000 | 4 (50) | 4 (50) | 7 |
| 18 |
|
|
13 | 41 | -- | 9 (40) | 11 (70) | 18 |
| 19 |
|
|
11 | 60 | 1473 | 16 (20) | 7 (40) | 12 |
| 20 |
|
|
16 | 39 | >10,000 | 13 (120) | 18 (210) | 55 |
| 21 |
|
|
>10,000 | -- | -- | >10,000 (26,020) | -- (26,020) | -- |
| 22 |
|
|
41 | 190 | 2934 | 30 (30) | 129 (330) | 125 |
| 23 |
|
|
183 | 429 | -- | 123 (5820) | 169 (1640) | 599 |
| 24 |
|
|
73 | 462 | 2663 | 60 (30) | 61 (150) | 93 |
| 25 |
|
|
(40) | (210) | ||||
| 26 |
|
|
102 | 345 | -- | 86 (130) | 107 (520) | 137 |
| 27 |
|
|
34 | 52 | >10,000 | 42 (70) | 10 (70) | 18 |
| 28 |
|
|
180 | 259 | -- | 75 (120) | 25 (130) | 42 |
| 29 |
|
|
1262 | >10,000 | -- | 5450 (370) | 273 (520) | 884 |
a
IC50 values in parentheses determined using Kinase Glo (Promega) qHTS assay. The remaining IC50 values determined by Reaction Biology (www.reactionbiology.com). Compounds were tested in 10-dose IC50 mode with 3-fold serial dilution starting at 10 μM. Reactions were carried out at 10 μM ATP.