Table 3.

Treatment of cells with chemotherapy followed by treatment with CEP-701



Cytarabine

Daunorubicin

Etoposide

Mitoxantrone

IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
MV4-11   302   0.369   0.503   98   0.823   0.506   1 801   0.362   0.230   17   0.373   0.247  
BaF3/ITD   1583   0.804   0.677   170   0.574   0.564   13 310   0.515   0.507   15   0.657   0.634  
AML/ITD   ND   ND   ND   117   0.882   0.921   21 000   0.729   0.688   15   0.839   0.909  
HL60
 
1325
 
1.068
 
1.074
 
366
 
0.928
 
1.021
 
14 470
 
0.927
 
0.946
 
119
 
1.120
 
0.937
 


Cytarabine

Daunorubicin

Etoposide

Mitoxantrone

IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
IC50, nM
CI, 10 nM
CI, 20 nM
MV4-11   302   0.369   0.503   98   0.823   0.506   1 801   0.362   0.230   17   0.373   0.247  
BaF3/ITD   1583   0.804   0.677   170   0.574   0.564   13 310   0.515   0.507   15   0.657   0.634  
AML/ITD   ND   ND   ND   117   0.882   0.921   21 000   0.729   0.688   15   0.839   0.909  
HL60
 
1325
 
1.068
 
1.074
 
366
 
0.928
 
1.021
 
14 470
 
0.927
 
0.946
 
119
 
1.120
 
0.937
 

Table shows IC50 and CI values for the combination of 10 nM or 20 nM CEP-701 and chemotherapeutic agents at doses corresponding to the approximate IC50. In this posttreatment scenario, cells were exposed to chemotherapy for 24 hours (cytarabine only), or 1 hour (daunorubicin, etoposide, or mitoxantrone), washed, and then transferred into medium containing CEP-701. MTT assays were then performed 48 hours later. Each CI value was obtained by conducting dose-response experiments for CEP-701 and the indicated chemotherapy individually and in combination over a range of doses for both drugs. ND indicates not determined.

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