Quantitative selectivity of FLT3 inhibitors
Compound . | S (3 μM) . | S (100 nM) . | S ([Kdoff-target/Kd FLT3] < 10) . |
---|---|---|---|
AC220 | 0.067 | 0.028 | 0.014 |
CEP-701 | 0.81 | 0.46 | 0.43 |
MLN-518 | 0.056 | 0.014 | 0.011 |
PKC-412 | 0.44 | 0.084 | 0.087 |
CGP-52421 | 0.19 | 0.031 | 0.089 |
Sorafenib | 0.18 | 0.045 | 0.042 |
Sunitinib | 0.58 | 0.19 | 0.020 |
Compound . | S (3 μM) . | S (100 nM) . | S ([Kdoff-target/Kd FLT3] < 10) . |
---|---|---|---|
AC220 | 0.067 | 0.028 | 0.014 |
CEP-701 | 0.81 | 0.46 | 0.43 |
MLN-518 | 0.056 | 0.014 | 0.011 |
PKC-412 | 0.44 | 0.084 | 0.087 |
CGP-52421 | 0.19 | 0.031 | 0.089 |
Sorafenib | 0.18 | 0.045 | 0.042 |
Sunitinib | 0.58 | 0.19 | 0.020 |
Selectivity scores were calculated as described,44 based on the data shown in supplemental Table 1 for 359 distinct kinases. Lower scores indicate greater selectivity. Mutant variants were not included in the calculation. S ([Kd off-target/Kd FLT3] < 10) is the fraction of kinases screened that bind with affinities within 10-fold or better of the affinity for FLT3.