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Paradox index of BRAFi
Compound
Paradox Index
(EC
80
/IC
80
)
Vemurafenib
5.5
Dabrafenib
10
Encorafenib
50
Adelmann et al., 2016, Oncotarget
The paradoxical index
in vitro
:
• Melanoma BRAFm cell line A375
Test on BRAFm : cell viability
• Melanoma BRAFwt cell line HaCaT
Test on BRAFwt : phospho-ERK
analysis
IC
80
EC
80
150
100
50
0
-10 -9 -8 -7 -6 -5 -4
Dabrafenib
b
9
8
7
6
5
4
3
2
1
0
IC
80
EC
80
150
100
50
0
-10 -9 -8 -7 -6 -5 -4
Vemurafenib
a
9
8
7
6
5
4
3
2
1
0
IC
80
EC
80
150
100
50
0
-10 -9 -8 -7 -6 -5 -4
Encorafenib
c
9
8
7
6
5
4
3
2
1
0
% Cell Viability
(A375)
Relative pERK/tERK (HaCaT HRAS
G12V
)
Log [Compound], M