Table 2.
Further in vitro kinase selectivity summary of lead compound 3a.[a]
| Kinases | IC50[nm] | SI[b] | |
|---|---|---|---|
| 3a | Staurosporine | ||
| ALK5/TGFBR1 | >100 000 | 10 100 | >2941 |
| Aurora A | 7900 | <1.0 | 232 |
| CDK1 cyclin B | 3250 | <1.0 | 96 |
| CDK2 cyclin E | 1800 | 1.3 | 53 |
| CDK3 cyclin E | 7090 | 5.4 | 209 |
| CDK4 cyclin D1 | 2970 | 6.1 | 87 |
| CDK5 p25 | 4220 | 2.4 | 124 |
| CDK6 cyclin D3 | 8180 | 17.2 | 241 |
| CDK7 cyclin H | – | 155 | – |
| CDK9 cyclin T1 | 8800 | 7.4 | 259 |
| DYRK1 B | 5970 | 6.3 | 176 |
| GSK3α | 37.6 | 2.8 | 1 |
| HIPK4 | 10 000 | 408 | 294 |
| MSK1 | 14 000 | <1.0 | 412 |
| PHKγ1 | 14 100 | 1.2 | 415 |
| PKCα | 45 700 | 1.6 | 1344 |
| PKCβ2 | 23 000 | <1.0 | 677 |
[a]
The compound was tested in ten-dose IC50 mode with three-fold serial dilution starting at 100 µm. Control compound staurosporine was tested in ten-dose IC50 mode with three-fold serial dilution starting at 20 µm. Reactions were carried out at 10 µm ATP. These compounds were tested by Reaction Biology, Inc. (http://www.reactionbiology.com).
[b]
Kinase selectivity index (SI) of compound 3a for GSK-3β over other kinases tested.