Supplementary Figure S1.
Supplementary Figure S1. Determination of the binding mode of the FGFR inhibitor
CH5183284/Debio 1347.
Lineweaver-Burk plot of FGFR1 with different concentrations of ATP in presence of various
concentrations of CH5183284/Debio 1347. Linear graphs intersected all with y-axis (i.e. Vmax
unchanged) which does support an ATP-competitive mode-of-action of CH5183284/Debio
1347 for FGFR1.
Supplementary Figure S2.
total vessel area (pixel number)
A.
B.
14000
(a)
(d)
(b)
(e)
12000
10000
8000
6000
4000
2000
(c)
0
0.1
1
DMSO CH5183284
(µM)
0.01
0.1
cediranib
(µM)
Supplementary Figure S2. Effects of CH5183284/Debio 1347 and cediranib on in vitro
VEGF-induced tube formation
(A) Inhibition of tube formation by CH5183284/Debio 1347 and cediranib in a HUVEC and
fibroblast co-culture system. Total vessel area was measured quantitatively for the area of
capillary-like tube formation with Kurabo angiogenesis image analysis software. N=3. (B)
Representative mages of tube formation of HUVEC. x4 objective. (a) DMSO treatment. (b)
0.1 µM of CH5183284/Debio 1347. (c) 1 µM of CH5183284/Debio 1347 . (d) 0.01 µM of
cediranib. (e) 0.1 µM of cediranib.
Relative kinase activity of FGFR2 to mock
Supplementary Figure S3.
10
8
6
4
2
0
mock
WT
V564F
V564I
V564L
Supplementary Figure S3. Kinase activity of FGFR2 WT, V564F, V564I, and V564L
mutants.
The 293 cells were transiently transfected with pCXND3 FGFR2 WT, FGFR2 V564F, FGFR2 V564I, and
FGFR2 V564L. The kinases were immunoprecipitated with anti-FGFR2 antibody. Then, kinase activity
was evaluated by examining their ability to phosphorylate substrate peptide using a time-resolved
fluorescence resonance energy transfer (TR-FRET) assay. (N=2)
Supplementary Figure S4.
CH5183284
AZD4547
0
0.01
0.03
0.1
0.3
1
3
10
0
0.001
0.003
0.01
0.03
0.1
0.3
1
(µM)
AZD4547
0
0.01
0.03
0.1
0.3
1
3
10
0
0.001
0.003
0.01
0.03
0.1
0.3
1
CH5183284
pY-FGFR
FGFR2
WT
V564F
V564I
V564L
Supplementary Figure S4. Inhibition of cellular pY-FGFR2 WT, pY-FGFR2 V564F, pYFGFR2 V564I, and pY-FGFR2 V564L.
The HCT-116 cells were transiently transfected with pCXND3 FGFR2 WT, FGFR2 V564F,
FGFR2 V564I, and FGFR2 V564L. A day after the transfection, the cells were treated with
the indicated concentration of CH5183284/Debio 1347 or AZD4547 for 2 h. Cells were
extracted and analyzed by Western blotting.
Supplementary Figure S5.
A.
% inhibition
PD173074
cediranib
120
100
80
60
40
20
0
-20
120
100
80
60
40
20
0
-20
-8
-6
-4
-2
0
2
Drug conc. μM ( log10)
WT clone1
WT clone3
V564F clone2
WT clone2
V564F clone1
V564F clone3
-8
-6
-4
-2
0
2
Drug conc. μM ( log10)
WT clone1
WT clone3
V564F clone2
WT clone2
V564F clone1
V564F clone3
B.
pY-FGFR
TEL-FGFR2
WT
V564F
Supplementary Figure S5. Susceptibility of CH5183284/Debio 1347 against
gatekeeper mutants of FGFR2.
(A) Anti-proliferative activity of PD173074 and cediranib against TEL-FGFR2 WT driven
Ba/F3 cells and TEL-FGFR2 V564F-driven Ba/F3 cells. Three clones were treated with
various concentrations of the indicated inhibitors for 4 days. The viable cells were counted
with WST-8.
(B) TEL-FGFR2 WT driven Ba/F3 and TEL-FGFR2 V564-driven Ba/F3 were treated with the
indicated 1 μM of CH5183284/Debio 1347, AZD4547, and NVP-BGJ398 for 2 hours. Cells
were extracted and analyzed by Western blotting.
Supplementary Figure S6.
CH5183284
Tumor volume (mm3)
A.
AZD4547
1000
1000
800
800
600
600
Vehicle
6.25 mg/kg 400
12.5 mg/kg
25 mg/kg
200
50 mg/kg
100 mg/kg
0
400
200
0
Vehicle
6.25 mg/kg
12.5 mg/kg
25 mg/kg
50 mg/kg
9 11 13 15 17 19
9 11 13 15 17 19
Days after the inoculation
Days after the inoculation
CH5183284
(mg/kg)
B.
Vehicle
50
100
AZD4547
(mg/kg)
25
50
pY-FGFR
TEL-FGFR2 WT
Actin
Supplementary Figure S6. Antitumor activity of CH5183284/Debio 1347 and AZD4547
in Ba/F3 TEL-FGFR2 WT-driven mouse model.
(A) Mice bearing Ba/F3 TEL-FGFR2 WT cells were treated with CH5183284/Debio 1347 or
AZD4547 orally once daily for 11 days at the indicated doses. Tumor volume and body
weight change for each dose group were measured. Data are shown as mean ± SD (n = 5).
(B) Suppression of phospho-FGFR inhibition in xenograft tissue. Mice bearing Ba/F3 TELFGFR2 WT cells were treated for 11 days at 50 and 100 mg/kg of CH5183284/Debio 1347
or 25 and 50 mg/kg of AZD4547, and xenograft tumors were extracted at 4 hours postdosing and analyzed by Western blotting. (n = 3)
Supplementary Figure S7.
120
120
120
100
100
100
80
% inhibition
% inhibition
CH5183284
80
60
40
20
0
-20
80
-3
-2
-1
0
1
40
40
系列1
N549H
20
0
0
-20
-5
-4
-6
-3 -4 -2
PD173074
120
100
100
100
60
40
20
0
% inhibition
120
80
80
60
40
20
0
-20
-3
-2
-1
0
Drug conc. μM ( log10)
80
60
40
20
0
-20
-4
0 0
Drug conc. μM ( log10)
120
-5
-1
-2
NVP-BGJ398
% inhibition
% inhibition
系列2
WT
20
Drug conc. μM ( log10)
AZD4547
60
60
-20
-4
dovitinib
-20
-4
-3
-2
-1
0
1
Drug conc. μM ( log10)
-4
-3
-2
-1
0
1
Drug conc. μM ( log10)
Supplementary Figure S7. Kinase inhibition assay of FGFR2 WT or FGFR2 N549H
mutant
Kinase inhibitory activity of FGFR inhibitors against FGFR2 WT or FGFR2 N549H were
measured (n=3). CH5183284, dovitinib, AZD4547, NVP-BGJ398, and PD173074 showed
12, 5.2, 26, 19, 30 fold higher IC50 against FGFR2 N549H than FGFR2 WT, respectively.
Supplementary Table S1.
Supplementary Table S1
Crystallographic data collection and refinement statistics for
FGFR1 in complex with CH5183284/Debio 1347.
Data collection
X-ray source
Wavelength [Å]
Detector
Temperature [K]
Resolution [Å]
Observed reflections
Unique reflections
Completeness [%]
Rsym [%]
Rmeas [%]
I/sigma(I)
Space group
Unit cell (a, b, c) [Å]
PXII/X10SA (SLS)
1.000
PILATUS 6M
100
47.1-2.02
2.13-2.02
163718
23073
48444
7015
99.3
99.1
3.3
69.6
4.4
93.2
14.9
1.5
C 12 1
211.21, 56.75, 65.45, 90, 107.43, 90
Refinement
Resolution
Number of reflections
(working/test)
Rcryst [%]
Rfree [%]
Number of atoms:
Protein
Ligand
Water
Phosphate ion
Deviation from ideal geometry:
Bond lengths [Å]
Bond angles [ °]
Ramachandran plot:
Most favoured regions
Additional allowed regions
Generously allowed regions
43.35-2.15
39318 / 1954
22.3
25.7
4460
54
75
5
0.010
1.03
92.2
7.0
0.8
Supplementary Table S2.
Supplementary Table S2
Kinase selectivity profile of CH5183284/Debio 1347. The values of %
competition at 0.1 or 1 μM CH5183284/Debio 1347 in DiscoveRx’s
KINOMEscan for 442 kinases including mutated kinases.
Kinase
AAK1
ABL1(E255K)-phosphorylated
ABL1(F317I)-nonphosphorylated
ABL1(F317I)-phosphorylated
ABL1(F317L)-nonphosphorylated
ABL1(F317L)-phosphorylated
ABL1(H396P)-nonphosphorylated
ABL1(H396P)-phosphorylated
ABL1(M351T)-phosphorylated
ABL1(Q252H)-nonphosphorylated
ABL1(Q252H)-phosphorylated
ABL1(T315I)-nonphosphorylated
ABL1(T315I)-phosphorylated
ABL1(Y253F)-phosphorylated
ABL1-nonphosphorylated
ABL1-phosphorylated
ABL2
ACVR1
ACVR1B
ACVR2A
ACVR2B
ACVRL1
ADCK3
ADCK4
AKT1
AKT2
AKT3
ALK
AMPK-alpha1
AMPK-alpha2
ANKK1
ARK5
ASK1
ASK2
AURKA
AURKB
AURKC
AXL
BIKE
BLK
BMPR1A
BMPR1B
BMPR2
BMX
BRAF
BRAF(V600E)
BRK
BRSK1
BRSK2
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
74
<65
<65
65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
72
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
85
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
BTK
CAMK1
CAMK1D
CAMK1G
CAMK2A
CAMK2B
CAMK2D
CAMK2G
CAMK4
CAMKK1
CAMKK2
CASK
CDC2L1
CDC2L2
CDC2L5
CDK11
CDK2
CDK3
CDK4-cyclinD1
CDK4-cyclinD3
CDK5
CDK7
CDK8
CDK9
CDKL1
CDKL2
CDKL3
CDKL5
CHEK1
CHEK2
CIT
CLK1
CLK2
CLK3
CLK4
CSF1R
CSK
CSNK1A1
CSNK1A1L
CSNK1D
CSNK1E
CSNK1G1
CSNK1G2
CSNK1G3
CSNK2A1
CSNK2A2
CTK
DAPK1
DAPK2
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
76
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
99
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
DAPK3
DCAMKL1
DCAMKL2
DCAMKL3
DDR1
DDR2
DLK
DMPK
DMPK2
DRAK1
DRAK2
DYRK1A
DYRK1B
DYRK2
EGFR
EGFR(E746-A750del)
EGFR(G719C)
EGFR(G719S)
EGFR(L747-E749del, A750P)
EGFR(L747-S752del, P753S)
EGFR(L747-T751del,Sins)
EGFR(L858R)
EGFR(L858R,T790M)
EGFR(L861Q)
EGFR(S752-I759del)
EGFR(T790M)
EIF2AK1
EPHA1
EPHA2
EPHA3
EPHA4
EPHA5
EPHA6
EPHA7
EPHA8
EPHB1
EPHB2
EPHB3
EPHB4
EPHB6
ERBB2
ERBB3
ERBB4
ERK1
ERK2
ERK3
ERK4
ERK5
ERK8
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
72
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
92
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
ERN1
FAK
FER
FES
FGFR1
FGFR2
FGFR3
FGFR3(G697C)
FGFR4
FGR
FLT1
FLT3
FLT3(D835H)
FLT3(D835Y)
FLT3(ITD)
FLT3(K663Q)
FLT3(N841I)
FLT3(R834Q)
FLT4
FRK
FYN
GAK
GCN2(Kin.Dom.2,S808G)
GRK1
GRK4
GRK7
GSK3A
GSK3B
HCK
HIPK1
HIPK2
HIPK3
HIPK4
HPK1
HUNK
ICK
IGF1R
IKK-alpha
IKK-beta
IKK-epsilon
INSR
INSRR
IRAK1
IRAK3
IRAK4
ITK
JAK1(JH1domain-catalytic)
JAK1(JH2domain-pseudokinase)
JAK2(JH1domain-catalytic)
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
90
87
80
85
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
100
97
99
99
<65
82
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
JAK3(JH1domain-catalytic)
JNK1
JNK2
JNK3
KIT
KIT(A829P)
KIT(D816H)
KIT(D816V)
KIT(L576P)
KIT(V559D)
KIT(V559D,T670I)
KIT(V559D,V654A)
LATS1
LATS2
LCK
LIMK1
LIMK2
LKB1
LOK
LRRK2
LRRK2(G2019S)
LTK
LYN
LZK
MAK
MAP3K1
MAP3K15
MAP3K2
MAP3K3
MAP3K4
MAP4K2
MAP4K3
MAP4K4
MAP4K5
MAPKAPK2
MAPKAPK5
MARK1
MARK2
MARK3
MARK4
MAST1
MEK1
MEK2
MEK3
MEK4
MEK5
MEK6
MELK
MERTK
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
92
<65
<65
<65
87
95
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
100
<65
<65
<65
99
100
<65
83
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
70
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
MET
MET(M1250T)
MET(Y1235D)
MINK
MKK7
MKNK1
MKNK2
MLCK
MLK1
MLK2
MLK3
MRCKA
MRCKB
MST1
MST1R
MST2
MST3
MST4
MTOR
MUSK
MYLK
MYLK2
MYLK4
MYO3A
MYO3B
NDR1
NDR2
NEK1
NEK11
NEK2
NEK3
NEK4
NEK5
NEK6
NEK7
NEK9
NIM1
NLK
OSR1
p38-alpha
p38-beta
p38-delta
p38-gamma
PAK1
PAK2
PAK3
PAK4
PAK6
PAK7
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
PCTK1
PCTK2
PCTK3
PDGFRA
PDGFRB
PDPK1
PFCDPK1(P.falciparum)
PFPK5(P.falciparum)
PFTAIRE2
PFTK1
PHKG1
PHKG2
PIK3C2B
PIK3C2G
PIK3CA
PIK3CA(C420R)
PIK3CA(E542K)
PIK3CA(E545A)
PIK3CA(E545K)
PIK3CA(H1047L)
PIK3CA(H1047Y)
PIK3CA(I800L)
PIK3CA(M1043I)
PIK3CA(Q546K)
PIK3CB
PIK3CD
PIK3CG
PIK4CB
PIM1
PIM2
PIM3
PIP5K1A
PIP5K1C
PIP5K2B
PIP5K2C
PKAC-alpha
PKAC-beta
PKMYT1
PKN1
PKN2
PKNB(M.tuberculosis)
PLK1
PLK2
PLK3
PLK4
PRKCD
PRKCE
PRKCH
PRKCI
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
76
92
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
99
100
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
PRKCQ
PRKD1
PRKD2
PRKD3
PRKG1
PRKG2
PRKR
PRKX
PRP4
PYK2
QSK
RAF1
RET
RET(M918T)
RET(V804L)
RET(V804M)
RIOK1
RIOK2
RIOK3
RIPK1
RIPK2
RIPK4
RIPK5
ROCK1
ROCK2
ROS1
RPS6KA4(Kin.Dom.1-N-terminal)
RPS6KA4(Kin.Dom.2-C-terminal)
RPS6KA5(Kin.Dom.1-N-terminal)
RPS6KA5(Kin.Dom.2-C-terminal)
RSK1(Kin.Dom.1-N-terminal)
RSK1(Kin.Dom.2-C-terminal)
RSK2(Kin.Dom.1-N-terminal)
RSK3(Kin.Dom.1-N-terminal)
RSK3(Kin.Dom.2-C-terminal)
RSK4(Kin.Dom.1-N-terminal)
RSK4(Kin.Dom.2-C-terminal)
S6K1
SBK1
SgK110
SGK3
SIK
SIK2
SLK
SNARK
SNRK
SRC
SRMS
SRPK1
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
91
94
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S2 (cont).
Kinase
SRPK2
SRPK3
STK16
STK33
STK35
STK36
STK39
SYK
TAK1
TAOK1
TAOK2
TAOK3
TBK1
TEC
TESK1
TGFBR1
TGFBR2
TIE1
TIE2
TLK1
TLK2
TNIK
TNK1
TNK2
TNNI3K
TRKA
TRKB
TRKC
TRPM6
TSSK1B
TTK
TXK
TYK2(JH1domain-catalytic)
TYK2(JH2domain-pseudokinase)
TYRO3
ULK1
ULK2
ULK3
VEGFR2
VRK2
WEE1
WEE2
YANK1
YANK2
YANK3
YES
YSK1
YSK4
ZAK
ZAP70
% competition at 100 nM % competition at 1000 nM
in KINOMEscan
in KINOMEscan
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
<65
Supplementary Table S3.
Supplementary Table S3
Selective antiproliferative activity of CH5183284/Debio 1347 against
cancer cell lines harboring genetic alterations in FGFR
Cell line
Tumor type
CH5183284
IC50 (µM)
SNU-16
Kato-III
HSC-39
AGS
HGC-27
MKN-1
MKN-45
SNU-1
JR-St
NCI-N87
NUGC-4
MKN-74
NUGC-3
SCH
MKN-28
SNU-5
MFE-296
AN3 CA
MFE-280
HEC-59
HEC-1-B
HEC-1-A
KLE
HEC-151
RL95-2
HEC-50B
HEC-108
RT112/84
UM-UC-14
SW780
RT4
T24
5637
J82
SCaBER
JMSU1
UM-UC-3
HT-1376
HT-1197
TCCSUP
BFTC-905
647-V
KMS-11
OPM-2
KMS-12-PE
KMS-26
KMS-21BM
NCI-H929
IM-9
KMS-34
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Gastric cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Endometrial cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Bladder cancer
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
0.017
0.018
0.050
2.9
3.0
3.0
5.0
5.0
7.1
10
>10
>10
>10
>10
>10
>10
0.042
0.054
0.41
2.8
5.7
9.2
10
10
>10
>10
>10
0.018
0.11
0.12
0.35
2.6
3.5
4.1
5.8
7.1
7.2
10
>10
>10
>10
>10
0.14
1.3
2.7
3.0
4.5
5.6
6.0
7.7
FGFR genetic alterations
FGFR2 gene amplification
FGFR2 gene amplification
FGFR2 gene amplification
FGFR2 N549K mutation
FGFR2 K310R/N549K mutation
FGFR2 S252W mutation
FGFR3-TACC3 fusion
FGFR3 S249C mutation
FGFR3-BAIAP2L1 fusion
FGFR3-TACC3 fusion
FGFR3 Y373C mutation
FGFR3 K650E mutation
FGFR3 F386L mutation
Supplementary Table S3 (cont).
Cell line
Tumor type
CH5183284
IC50 (µM)
KMM-1
KMS-12-BM
KHM-1B
LP-1
KMS-20
L-363
KMS-28BM
NCI-H520
PC-1
HARA
HARA-B
NCI-H226
QG-56
NCI-H2170
Calu-1
PC-10
SK-MES-1
NCI-H1703
PC-9
HCC78
ABC-1
NCI-H1395
NCI-H23
NCI-H2009
NCI-H1755
NCI-H1568
NCI-H2122
NCI-H838
NCI-H1355
NCI-H1944
COR-L105
SK-LU-1
NCI-H1437
HCC827
NCI-H2347
NCI-H522
NCI-H1993
NCI-H1792
A549
NCI-H2023
NCI-H1975
NCI-H2228
Calu-3
NCI-H2030
NCI-H1838
NCI-H1793
NCI-H1581
NCI-H292
NCI-H1155
NCI-H1666
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Multiple Myeloma
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Squamouse
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Adenocarcinoma
Non-small cell lung cancer, Large cell
Non-small cell lung cancer, Mucoepidermoid
Non-small cell lung cancer, Large cell
Non-small cell lung cancer, Bronchiolo-Alveolar
8.6
>10
>10
>10
>10
>10
>10
0.30
1.3
9.1
9.8
>10
>10
>10
>10
>10
>10
0.79
2.8
5.0
5.5
5.9
6.0
6.8
8.0
9.2
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
0.22
1.9
2.1
5.3
FGFR genetic alterations
FGFR1 gene amplification
FGFR2 V12M mutation
FGFR1 gene amplification
FGFR1 gene amplification
Supplementary Table S3 (cont).
Cell line
Tumor type
NCI-H596
Non-small cell lung cancer, Adenosquamous
NCI-H2110
Non-small cell lung cancer
Calu-6
Non-small cell lung cancer
NCI-H661
Non-small cell lung cancer, Large cell
NCI-H460
Non-small cell lung cancer, Large cell
NCI-H441
Non-small cell lung cancer, Papillary
HCC366
Non-small cell lung cancer, Adenosquamous
PC-13
Non-small cell lung cancer, Large cell
NCI-H1299
Non-small cell lung cancer, Large cell
NCI-H1650
Non-small cell lung cancer, Bronchiolo-Alveolar
NCI-H1781
Non-small cell lung cancer, Bronchiolo-Alveolar
LCLC-103H
Non-small cell lung cancer, Large cell
DMS 114
Small cell lung cancer
NCI-H2227
Small cell lung cancer
NCI-H82
Small cell lung cancer
SHP-77
Small cell lung cancer
NCI-H526
Small cell lung cancer
NCI-H1930
Small cell lung cancer
DMS 53
Small cell lung cancer
SUM-52PE
Breast cancer
MFM-223
Breast cancer
HCC2218
Breast cancer
MCF10DCIS.com
Breast cancer
MDA-MB-157
Breast cancer
DU-4475
Breast cancer
Hs 578.T
Breast cancer
MCF10A
Breast normal
HCC38
Breast cancer
SUM-44PE
Breast cancer
SUM-229PE
Breast cancer
MDA-MB-453
Breast cancer
MDA-MB-468
Breast cancer
MCF7
Breast cancer
HCC1500
Breast cancer
HCC1187
Breast cancer
MDA-MB-175-VII
Breast cancer
CAL-120
Breast cancer
HCC1569
Breast cancer
HCC1599
Breast cancer
ZR-75-1
Breast cancer
MDA-MB-231
Breast cancer
JIMT-1
Breast cancer
CAMA-1
Breast cancer
HCC1395
Breast cancer
BT-474
Breast cancer
HCC1806
Breast cancer
HCC70
Breast cancer
HCC1954
Breast cancer
T47D
Breast cancer
HCC1419
Breast cancer
CH5183284
IC50 (µM)
6.1
6.9
8.2
8.6
8.9
>10
>10
>10
>10
>10
>10
>10
0.18
1.4
2.6
5.6
8.7
>10
>10
0.018
0.058
1.2
1.6
2.3
3.1
3.7
6.2
6.4
6.9
7.4
7.7
8.0
8.4
8.6
9.2
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
FGFR genetic alterations
FGFR1 gene amplification
FGFR2 gene amplification
FGFR2 gene amplification
FGFR1 gene amplification
FGFR1 gene amplification
FGFR1 gene amplification
FGFR1 gene amplification
FGFR1 gene amplification
FGFR1 S125L mutation
Supplementary Table S3 (cont).
Cell line
Tumor type
CH5183284
IC50 (µM)
ZR-75-30
HCC1937
SK-BR-3
HCC1428
COLO-824
UACC-812
HCC1143
MDA-MB-361
BT-20
MDA-MB-134-VI
BT-483
NCI-H716
COLO-205
HCT-8
CaR-1
SW48
LS174T
LS513
HT-29
COLO-201
NCI-H508
SW620
RKO
SW480
LS411N
HCT-116
LS1034
HCT-15
WiDr
CW-2
T84
SW948
SW1417
DLD-1
SW1463
LoVo
SW403
Caco-2
COLO-320DM
SW1116
KG-1
KG-1a
MV-4-11
NB-4
10C9
MOLM-13
Raji
Ramos
MEG-01
MC/CAR
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Colorectal cancer
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Acute
Leukemia, Biphenotypic, Acute
Leukemia, Promyelocytic, Acute
Lymphoma, Non-Hodgkin
Leukemia, Myeloid, Acute
Burkitt Lymphoma
Burkitt Lymphoma
Leukemia, Myelogenous, Chronic
Plasmacytoma
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
0.013
2.9
3.2
5.8
5.9
7.5
7.9
7.9
7.9
8.3
8.3
8.7
8.8
9.0
10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
0.014
0.030
1.9
2.1
2.3
2.5
3.1
3.5
4.1
4.1
FGFR genetic alterations
FGFR1 gene amplification
FGFR2 gene amplification
FGFR1OP-FGFR1 fusion
FGFR1OP-FGFR1 fusion
Supplementary Table S3 (cont).
Cell line
Tumor type
CH5183284
IC50 (µM)
KARPAS-299
U-698-M
K-562
CMK-11-5
ARH-77
NKM-1
U-937
SR
SU-DHL-1
HEL
U266B1
CEM/C2
TF-1a
CCRF-CEM
RPMI-8226
NOMO-1
HL-60
HDLM-2
F-36P
THP-1
SKM-1
HMCB
SK-MEL-5
A2058
A-375
SK-MEL-30
SK-MEL-1
SK-MEL-28
MDA-MB-435S
MeWo
A-431
SK-MEL-2
C32
HuH-7
HuH-1
HepG2
PLC/PRF/5
Hep3B
SK-HEP-1
HLE
Hs 38.T
OVMANA
RMG-I
ES2
PA-1
COLO-704
SW626
SK-OV-3
OVCAR-3
MCAS
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell
Leukemia, Myelogenous, Chronic
Leukemia, Megakaryoblastic, Acute
Leukemia
Leukemia, Myeloid, Acute
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-Cell, Anaplastic
Leukemia, Erythroblastic, Acute
Plasmacytoma
Leukemia, T-Cell
Leukemia, Erythroblastic, Acute
Leukemia
Plasmacytoma
Leukemia, Myeloid, Acute
Leukemia, Promyelocytic, Acute
Lymph Nodes
Leukemia, Myeloid, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Melanoma
Melanoma
Melanoma
Melanoma
Melanoma
Melanoma
Melanoma
Melanoma
Melanoma
Skin cancer, Squamous Cell
Melanoma
Melanoma
Liver cancer
Liver cancer
Liver cancer
Liver cancer
Liver cancer
Liver cancer
Liver cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
Ovarian cancer
4.1
4.4
5.0
5.1
5.6
5.7
6.1
6.2
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
0.94
3.0
4.1
5.4
5.5
8.9
>10
>10
>10
>10
>10
>10
3.0
5.3
>10
>10
>10
>10
>10
2.3
2.7
5.9
6.2
9.5
>10
>10
>10
>10
>10
FGFR genetic alterations
FGFR2 E636K mutation
Supplementary Table S3 (cont).
Cell line
Tumor type
CH5183284
IC50 (µM)
EFO-21
HPAC
KP-4
YAPC
Mia PaCa-2
Panc-1
BxPC-3
HuP-T4
SU.86.86
Capan-1
HPAF-II
CFPAC-1
Capan-2
AsPC-1
Hs 766.T
A-172
NCCIT
SW579
U-2197
NTERA-2
CCF-STTG1
KYSE-150
D-341MED
NB-1
HT-1080
C-33 A
COLO-684
IMR-32
KYSE-70
TT
143B
SK-N-DZ
RPMI-2650
SH-SY5Y
Ca Ski
SJCRH30
SCC-9
T98G
Daoy
786-O
D-283MED
OE19
NCI-H358
EGI-1
KYSE-520
U-138 MG
SK-N-SH
LN-18
SK-N-F1
RH-30
Ovarian cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Pancreas cancer
Glioblastoma
Teratocarcinoma
Thyroid cancer
Histiocytoma
Teratocarcinoma
Astrocytoma
Esophageal cancer
Medulloblastoma
Neuroblastoma
Fibrosarcoma
Cervix cancer
Uterus cancer
Neuroblastoma
Esophageal cancer
Thyroid cancer
Osteosarcoma
Neuroblastoma
Nasal cancer
Neuroblastoma
Cervix cancer
Rhabdomyosarcoma
Tongue cancer
Glioblastoma
Medulloblastoma
Renal cancer
Medulloblastoma
Esophageal cancer
Bronchial cancer
Cholangiocarcinoma
Esophageal cancer
Glioblastoma
Neuroblastoma
Glioblastoma
Neuroblastoma
Rhabdomyosarcoma
>10
1.4
5.5
5.9
7.7
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
0.31
0.44
0.85
1.1
1.1
1.2
1.3
1.6
1.8
1.8
2.0
2.0
2.2
2.3
2.9
2.9
3.7
3.8
4.0
4.2
4.3
4.4
4.5
5.5
6.0
6.1
6.4
6.6
8.1
8.3
9.8
9.8
9.9
9.9
10
FGFR genetic alterations
Supplementary Table S3 (cont).
Cell line
Tumor type
CH5183284
IC50 (µM)
SK-ES-1
Detroit 562
CAL-27
NCI-H28
SK-N-AS
KELLY
HuH-28
ACHN
Caki-1
A-204
ME-180
SNG-M
SCC-25
A-673
PC-3
SCC-15
SCC-4
22Rv1
U-118 MG
8305C
DU-145
U-87 MG
VCaP
MG-63
Y79
RB247c
WERI-Rb-1
Ewing sarcoma
Pharynx cancer
Tongue cancer
Mesothelioma
Neuroblastoma
Neuroblastoma
Cholangiocarcinoma
Renal cancer
Renal cancer
Rhabdomyosarcoma
Cervix cancer
Uterus cancer
Tongue cancer
Rhabdomyosarcoma
Prostate cancer
Tongue cancer
Tongue cancer
Prostate cancer
Glioblastoma
Thyroid cancer
Prostate cancer
Glioblastoma
Prostate cancer
Osteosarcoma
Retinoblastoma
Retinoblastoma
Retinoblastoma
10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
>10
FGFR genetic alterations