Table 3.

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.

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