Table 1.

Biochemical profile of NVP-BEZ235 against selected protein kinases and class I PI3Ks

EnzymeIC50 (nmol/L)EnzymeIC50 (nmol/L)
Class I PI3Kp110α4 ± 2 (n = 3)p110β75 ± 45 (n = 3)
p110α-H1047R4.6 ± 0.8 (n = 3)p110δ7 ± 6 (n = 3)

p110α-E545K
5.7 ± 1.0 (n = 3)
p110γ
5 ± 4 (n = 3)
VEGFR1/Flt1>10,000 (n = 3)Fak>10,000 (n = 3)
Flt3>10,000 (n = 3)Jak2>10,000/9,000
HER1/ErbB1>10,000/8,500c-Abl>10,000 (n = 3)
IGFI-R>10,000 (n = 2)c-Src>10,000 (n = 3)
Protein kinasesEphB4>10,000 (n = 3)PKA>10,000 (n = 3)
Ret>10,000 (n = 3)Akt1/PKBα>10,000 (n = 3)
Tie-2/Tek>10,000 (n = 3)PDK1>10,000 (n = 2)
c-Met>10,000 (n = 3)V599E-B-Raf>10,000 (n = 3)
K650E-FGFR>10,000 (n = 3)CDK1>10,000 (n = 3)
  • NOTE: In vitro kinase assays were done with the indicated recombinant PI3K lipid or protein kinases in the presence of increasing concentrations of NVP-BEZ235 as described in Materials and Methods. The concentration responsible of 50% inhibition of the activity (IC50) is reported as average ± 1 SD (nmol/L).