Table 1.
Specificity and potency of compounds kinase inhibitor
| IC50 of compounds on RTKs (μM)
|
||||||||
|---|---|---|---|---|---|---|---|---|
| TKI258 | A1 | A2 | A3 | A5 | B2 | B5 | C2 | |
| FLT3 | 0.001 | >100 | >100 | >100 | >100 | >100 | >100 | >100 |
| FGFR1 | 0.008 | 23.24±1.12*** | 21.55±2.24*** | 25.32±1.89*** | 15.33±0.68** | 26.12±1.32** | 26.65±1.61*** | 25.65±1.53*** |
| FGFR2 | >10 | >100 | >100 | >100 | >100 | >100 | >100 | >100 |
| FGFR3 | 0.009 | 89.62±3.32*** | 75.12±2.56*** | 77.68±2.37*** | >100 | >100 | >100 | 94.50±2.62*** |
| PDGFR-β | 0.027 | >100 | 55.36±1.72*** | 66.89±2.06*** | >100 | >100 | 89.45±3.56*** | >100 |
| EGFR | 2 | >100 | >100 | >100 | >100 | >100 | >100 | >100 |
| Selectivity ratioa | 8 | 3.86 | 2.57 | 2.64 | 9.34 | 3.98 | 3.36 | 3.68 |
Notes: Each value represents the mean ± SEM from three experiments significantly different from TKI258 at
**
P≤0.005 and
***
P≤0.001 (Student’s t-test). A5 shows the most active compound. The concentration of TKI258 resulting in IC50 is obtained from the literature.25
a
Selectivity ratio is calculated by taking the ratio of the second lowest IC50 against the lowest IC50 value (ie, the two strongest binding targets).28
Abbreviation: SEM, standard error of the mean.