Table 1. Cross-Reactivity Profile of the Initial VEGFR-2 Lead Class.
| compd | R1 | R2 | X | ITPa IC50 (μM) | G2/M blockb EC50 (μM) | VEFGR-2 enzyme IC50 (μM) | VEGFR-2 cell IC50 (μM) |
|---|---|---|---|---|---|---|---|
| 1 | 3-trifluoromethyl | pyridin-4-yl | NH | >10 | >10 | 1.1 ± 0.14 | 1.0 ± 0.19 |
| 2 | 3-trifluoromethyl | pyrazol-4-yl | NH | >10 | >10 | >10 | >10 |
| 3 | 3-trifluoromethyl | pyridin-4-yl | O | >10 | >10 | 2.5 ± 0.14 | >10 |
| 4 | benzo[1,3]dioxol-5-yl | pyridin-4-yl | NH | >10 | >10 | 2.3 ± 0.06 | >10 |
| 5 | 4-methylsulfonyl | 1,4-dioxan-2-yl | NH | 6.6 ± 0.07 | >10 | 4.5 ± 0.14 | >10 |
a
Compound concentration required for 50% inhibition of maximum tubulin assembly.
b
Compound concentration required for 50% of A431 cells to accumulate at the G2/M phase of the cell cycle.