Combination of 2 selective FLT3 PTK inhibitors has additive cytotoxic activity in Ba/F3 FLT3-ITD cells
. | . | Ci values at . | . | . | ||
---|---|---|---|---|---|---|
. | IC50 . | IC50 . | IC75 . | IC90 . | ||
SU5614, μM | 0.17 | NA | NA | NA | ||
PKC412, nM | 7.3 | NA | NA | NA | ||
SU5614, μM + PKC412, nM | 0.11 + 2.5 | 1.0 | 1.0 | 1.1 |
. | . | Ci values at . | . | . | ||
---|---|---|---|---|---|---|
. | IC50 . | IC50 . | IC75 . | IC90 . | ||
SU5614, μM | 0.17 | NA | NA | NA | ||
PKC412, nM | 7.3 | NA | NA | NA | ||
SU5614, μM + PKC412, nM | 0.11 + 2.5 | 1.0 | 1.0 | 1.1 |
IC50 values were determined as described in Table 2 and Figure 4. To assess combined drug effects, SU5614 and PKC412 were added simultaneously to cells in culture medium. The combination indices were evaluated by solving the equation Ci=[(D)1/(Dx)1] + [(D)2/(Dx)2] as described previously.47 (Dx)1 is the concentration of drug 1 required to produce an x percent effect of that drug alone. (D)1 is the concentration of drug 1 required to produce the same x percent effect in combination with (D)2. A combination index (Ci) less than 1 indicates synergy, a value more than 1 indicates antagonism, and a value of 1 indicates an additive effect. All values represent means of 3 independent experiments. NA indicates not applicable.