Table 3.
Discrimination of protein kinases with micromolar or nanomolar affinities for pyrido[2,3-d]pyrimidine derivatives by kinDOCK
| PD166326 (Predicted) | PD173955 (Predicted) | <PD> (Predicted) | pIC50(PP58) (Experimental) | |
|---|---|---|---|---|
| Mek1 bound to ATP (PDB1S9J) | 5.8 | 5.6 | 5.7 | 5.3 |
| Epha2r bound to AMP-PNP (PDB1MQB) | 5.7 | 6.7 | 6.2 | 5.4 |
| Ephb2r bound to adenine (PDB1JPA) | 5.7 | 8.5 | 7.1 | 8.0 |
| p38 inhibited form (PDB1DI9) | 5.0 | 10.0 | 7.5 | 8.3 |
| C-abl bound to STI-571 (PDB1IEP) | 8.5 | 9.8 | 9.1 | 9.3 |
| C-abl bound to PD173955 (PDB1M52) | 10.2 | 11.7 | 10.9 | 9.3 |
| Csk bound to staurosporine (PDB1BYG) | 10.2 | 10.5 | 10.3 | 9.4 |
The affinities of the PP58 (a pyrido[2,3-d]pyrimidine derivative related to PD166326 and PD173955) for each of the different protein kinases are deduced from experimental data (19). The mean predicted affinity score for the PD166326 and PD173955 ligands is shown in the <PD> column. The proteins in bold are the one with nanomolar affinities for PP58.