Table 1.

Biochemical profile of NVP-BKM120 against selected protein kinases, class I and IV PI3Ks, and PI4Kβ

EnzymeIC50, nmol/LEnzymeIC50, nmol/L
Class I PI3Ksa
 p110αk52 ± 37 (n = 7)p110β166 ± 29 (n = 3)
 p110α-H1047R58 ± 2 (n = 2)p110δ116 (n = 1)
 p110α-E545K99 ± 6 (n = 2)p110γ262 ± 94 (n = 7)
Class III
 Vps34b2,410 ± 150 (n = 19)
Class IV PI3Ks
 mTORc2,866 ± 1,671DNA-PKa>10,000
 ATRd8,091 ± 2,038
PI4K
 PI4Kβb>25,000 (n = 22)
Protein kinases
 Axl>10,000Fak>10,000
 VEGFR2/Kdr>10,000Jak2>10,000
 HER1/ErbB1>10,000c-Abl>10,000
 IGF1-R>10,000c-Src>10,000
 EphB4>10,000PKA>10,000
 Ret>10,000Akt1/PKBα>10,000
 Tie-2/Tek>10,000PDK1>10,000
 c-Met>10,000B-RafV599E9,200
 K650E-FGFR->10,000CDK2/cyclin A>10,000
 CSF1R582

NOTE: In vitro kinase assays were conducted with the indicated recombinant PI3K lipid or protein kinases, in the presence of increasing concentrations of NVP-BKM120, as described in Materials and Methods. The concentration responsible for 50% inhibition of the activity is reported (IC50) in nmol/L as determined in multiple experiments (n) is shown as an average ± one SD.

  • aFilter binding assay format.

  • bKinase-Glo format.

  • cTR-FRET assay format.

  • dAlpha Screen assay format.