Table 2. Promiscuity of the Three Considered Kinase Inhibitors.
We assumed rapid binding because these are small molecules, and calculated off rate constants based on published affinity data. We implemented a 10 uM Kd threshold.
| Drug | Gene Targets | Model Targets | k_on (1/s/nM) | k_off (1/s) |
|---|---|---|---|---|
| Bosutinib | MAP2K1/MAP2K2 | MEK | 1 | 288 |
| RPS6KA1/RPS6KA3 | RSK | 1 | 1115 | |
| PRKCA/PRKCG | PKC | 1 | 1567 | |
| CHEK1 | Chk1 | 1 | 1168 | |
| FGFR1 | Fr | 1 | 2206 | |
| IGF1R | Ir | 1 | 2285 | |
| INSR | Isr | 1 | 669 | |
| PDGFRA | Pr | 1 | 3081 | |
|
| ||||
| Ibrutinib | BRAF | Braf | 1 | 1128 |
| EGFR | E1 | 1 | 18 | |
| ERBB3 | E3 | 1 | 1 | |
| FGFR1/FGFR2 | Fr | 1 | 707 | |
| GSK3B | GSK3b | 1 | 2571 | |
| IGF1R | Ir | 1 | 4882 | |
| INSR | Isr | 1 | 1326 | |
| MTOR | mTOR | 1 | 8091 | |
| PDPK1 | PDK1 | 1 | 2448 | |
| PIK3CA/PIK3CB/PIK3CD/PIK3CG | PI3KC1 | 1 | 2039 | |
| RAF1 | Craf | 1 | 2333 | |
| RPS6KA1/RPS6KA3/RPS6KA2 | RSK | 1 | 6447 | |
|
| ||||
| Cabozantinib | BRAF | Braf | 1 | 2961 |
| EGFR | E1 | 1 | 864 | |
| FGFR1/FGFR2 | Fr | 1 | 2153 | |
| IGF1R | Ir | 1 | 8236 | |
| INSR | Isr | 1 | 1880 | |
| MAP2K1 | MEK | 1 | 214 | |
| MET | MET | 1 | 1 | |
| PDGFRA | Pr | 1 | 1 | |
| PIK3CA | PI3KC1 | 1 | 1084 | |
| PIK3R1 | PI3KR1 | 1 | 1084 | |
| RAF1 | Craf | 1 | 1078 | |