Table 1.

Biochemical IC50 determinations for PLX4720 versus a panel of kinases

AssayIC50, nM
B-Raf V600E13
B-Raf160
BRK130
FRK1,300
CSK1,500
SRC1,700
FAK1,700
FGFR1,900
KDR2,300
HGK2,800
CSF1R3,300
AURORA A3,400
  • Kinases with IC50s > 5,000 nM: ABL1, AKT1, AKT2, AKT3, ALK, BTK, CAMK2A, CDK2/CYCLIN A, CHK1, CHK2, CK1ε, CLK1, EGFR, EPHA2, EPHB4, ERK2, FER, FLT3, GRK2, GSK3β, HCK, IGF1R, IKKβ, IRAK4, JAK3, JNK1, JNK2, JNK3, KIT, MAPKAPK2, MEK1, MER, MET, MKK6, MLK1, MST1, NEK2, P38α, P70S6K, PAK3, PDGFRα, PDK1, PIM1, PKA, PKCμ, PKCθ, PLK1, PYK2, ROCK1, SYK, TAO1, TIE2, TRKA, TSSK1, ZIPK. We are unable to reliably measure wild-type c-Raf-1 activity. However, by using an activated form of c-Raf-1 with Y340D and Y341D mutations, an IC50 of 6.7 nM is determined. This suggests that PLX4720 binds with high affinity to the ″active″ form of both B-Raf and c-Raf-1.