Table 3.
Protein kinase selectivity of synthetic products derived from polyandrocarpamines A and B. All compounds were tested at various concentrations on 16 purified kinases (14 mammalian and two unicellular parasites). IC50 values, calculated from the dose-response curves, are reported in μM. IC50 values below 1 μM are shown in bold. PAC1 and PAC2, PAC12 and PAC13 are synthetic and natural polyandrocarpamines A and B, respectively.
| Kinases | Polyandrocarpamines (PAC) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | |
| CDK1/cyclin B | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 |
| CDK2/cyclin A | >10 | >10 | ≥10 | ≥10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 |
| CDK5/p25 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 |
| CDK9/cyclin T | 1.1 | 2 | >10 | >10 | ≥10 | >10 | >10 | 0.51 | >10 | >10 | >10 | 0.9 | 1.8 |
| CK1δ/ε | 5.2 | >10 | ≥10 | ≥10 | >10 | >10 | >10 | >10 | 3.6 | >10 | >10 | 5 | >10 |
| CLK1 | 0.43 | 1 | 2.2 | ≥10 | 2.2 | >10 | >10 | >10 | ≥10 | >10 | 4.2 | 0.47 | 0.59 |
| CLK2 | 1.2 | 2.5 | 6.3 | >10 | 7.5 | >10 | >10 | >10 | >10 | >10 | ≥10 | 0.64 | 2.42 |
| CLK3 | 2.3 | 9.2 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | 2.7 | 10 |
| CLK4 | 0.4 | 0.95 | 2.3 | ≥10 | 2.4 | >10 | >10 | >10 | >10 | >10 | 3.2 | 0.47 | 0.91 |
| DYRK1A | 0.23 | 0.75 | 2.1 | 4 | 1.3 | >10 | >10 | >10 | >10 | 3 | 2.1 | 0.3 | 0.59 |
| DYRK1B | 0.4 | 1.1 | 8.2 | >10 | 6.1 | >10 | >10 | >10 | >10 | >10 | 6.2 | 0.47 | 0.96 |
| DYRK2 | 0.14 | 0.48 | 2.2 | 4.5 | 0.64 | >10 | >10 | >10 | >10 | 3.4 | 1.3 | 0.24 | 0.38 |
| DYRK3 | 0.28 | 0.9 | >10 | 5.1 | 5.7 | >10 | >10 | >10 | >10 | >10 | 2.4 | 0.34 | 0.68 |
| GSK-3α/β | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | 2 | >10 | >10 |
| PfGSK-3 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 |
| LmCK1 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | >10 | 0.63 | >10 | >10 | >10 | >10 |