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 S1.

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.

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(a)

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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)

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Supplementary Figure S4. Inhibition of cellular pY-FGFR2 WT, pY-FGFR2 V564F, pY-FGFR2 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.

WT

V564F

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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.

A.

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WT clone1 WT clone2

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Actin

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Vehicle 50 100 5025

CH5183284(mg/kg)

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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 TEL-

FGFR2 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 post-dosing and analyzed by Western blotting. (n = 3)

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Vehicle6.25 mg/kg12.5 mg/kg25 mg/kg50 mg/kg100 mg/kg

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Supplementary Figure S7. Kinase inhibition assay of FGFR2 WT or FGFR2 N549H mutantKinase 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.

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Supplementary Table S1Crystallographic data collection and refinement statistics for FGFR1 in complex with CH5183284/Debio 1347.

Data collection

X-ray source PXII/X10SA (SLS) Wavelength [Å] 1.000 Detector PILATUS 6M Temperature [K] 100 Resolution [Å] 47.1-2.02 2.13-2.02 Observed reflections 163718 23073 Unique reflections 48444 7015 Completeness [%] 99.3 99.1 Rsym [%] 3.3 69.6 Rmeas [%] 4.4 93.2 I/sigma(I) 14.9 1.5 Space group C 1 2 1

Unit cell (a, b, c) [Å] 211.21, 56.75, 65.45, 90, 107.43, 90

Refinement

Resolution 43.35-2.15 Number of reflections (working/test)

39318 / 1954

Rcryst [%] 22.3 Rfree [%] 25.7 Number of atoms:

Protein 4460Ligand 54Water 75Phosphate ion 5

Deviation from ideal geometry: Bond lengths [Å] 0.010Bond angles [ °] 1.03

Ramachandran plot: Most favoured regions 92.2 Additional allowed regions 7.0 Generously allowed regions 0.8

Supplementary Table S1.

Supplementary Table S2Kinase 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% competition at 100 nM

in KINOMEscan% competition at 1000 nM

in KINOMEscan

AAK1 <65 <65ABL1(E255K)-phosphorylated <65 <65

ABL1(F317I)-nonphosphorylated <65 <65ABL1(F317I)-phosphorylated <65 <65

ABL1(F317L)-nonphosphorylated <65 <65ABL1(F317L)-phosphorylated <65 <65

ABL1(H396P)-nonphosphorylated <65 74ABL1(H396P)-phosphorylated <65 <65ABL1(M351T)-phosphorylated <65 <65

ABL1(Q252H)-nonphosphorylated <65 65ABL1(Q252H)-phosphorylated <65 <65

ABL1(T315I)-nonphosphorylated <65 <65ABL1(T315I)-phosphorylated <65 <65ABL1(Y253F)-phosphorylated <65 <65

ABL1-nonphosphorylated <65 <65ABL1-phosphorylated <65 <65

ABL2 <65 <65ACVR1 <65 <65

ACVR1B <65 <65ACVR2A <65 <65ACVR2B <65 72ACVRL1 <65 <65ADCK3 <65 <65ADCK4 <65 <65AKT1 <65 <65AKT2 <65 <65AKT3 <65 <65ALK <65 <65

AMPK-alpha1 <65 <65AMPK-alpha2 <65 <65

ANKK1 <65 <65ARK5 <65 <65ASK1 <65 <65ASK2 <65 <65

AURKA <65 <65AURKB <65 <65AURKC <65 <65

AXL <65 <65BIKE <65 <65BLK <65 85

BMPR1A <65 <65BMPR1B <65 <65BMPR2 <65 <65

BMX <65 <65BRAF <65 <65

BRAF(V600E) <65 <65BRK <65 <65

BRSK1 <65 <65BRSK2 <65 <65




in KINOMEscan

BTK <65 <65CAMK1 <65 <65

CAMK1D <65 <65CAMK1G <65 <65CAMK2A <65 <65CAMK2B <65 <65CAMK2D <65 <65CAMK2G <65 <65CAMK4 <65 <65

CAMKK1 <65 <65CAMKK2 <65 <65

CASK <65 <65CDC2L1 <65 <65CDC2L2 <65 <65CDC2L5 <65 <65CDK11 <65 <65CDK2 <65 <65CDK3 <65 <65

CDK4-cyclinD1 <65 <65CDK4-cyclinD3 <65 <65

CDK5 <65 <65CDK7 <65 <65CDK8 <65 <65CDK9 <65 <65CDKL1 <65 <65CDKL2 <65 <65CDKL3 <65 <65CDKL5 <65 <65CHEK1 <65 <65CHEK2 <65 <65

CIT <65 <65CLK1 <65 <65CLK2 <65 <65CLK3 <65 <65CLK4 <65 <65

CSF1R 76 99CSK <65 <65

CSNK1A1 <65 <65CSNK1A1L <65 <65CSNK1D <65 <65CSNK1E <65 <65

CSNK1G1 <65 <65CSNK1G2 <65 <65CSNK1G3 <65 <65CSNK2A1 <65 <65CSNK2A2 <65 <65

CTK <65 <65DAPK1 <65 <65DAPK2 <65 <65

Supplementary Table S2 (cont).



in KINOMEscan

DAPK3 <65 <65DCAMKL1 <65 <65DCAMKL2 <65 <65DCAMKL3 <65 <65

DDR1 <65 72DDR2 <65 <65DLK <65 <65

DMPK <65 <65DMPK2 <65 <65DRAK1 <65 <65DRAK2 <65 <65

DYRK1A <65 <65DYRK1B <65 <65DYRK2 <65 <65EGFR <65 <65

EGFR(E746-A750del) <65 <65EGFR(G719C) <65 <65EGFR(G719S) <65 <65

EGFR(L747-E749del, A750P) <65 <65EGFR(L747-S752del, P753S) <65 <65

EGFR(L747-T751del,Sins) <65 <65EGFR(L858R) <65 <65

EGFR(L858R,T790M) <65 <65EGFR(L861Q) <65 <65

EGFR(S752-I759del) <65 <65EGFR(T790M) <65 <65

EIF2AK1 <65 <65EPHA1 <65 <65EPHA2 <65 <65EPHA3 <65 <65EPHA4 <65 <65EPHA5 <65 <65EPHA6 <65 <65EPHA7 <65 <65EPHA8 <65 <65EPHB1 <65 <65EPHB2 <65 <65EPHB3 <65 <65EPHB4 <65 <65EPHB6 <65 92ERBB2 <65 <65ERBB3 <65 <65ERBB4 <65 <65ERK1 <65 <65ERK2 <65 <65ERK3 <65 <65ERK4 <65 <65ERK5 <65 <65ERK8 <65 <65




in KINOMEscan

ERN1 <65 <65FAK <65 <65FER <65 <65FES <65 <65

FGFR1 90 100FGFR2 87 97FGFR3 80 99

FGFR3(G697C) 85 99FGFR4 <65 <65

FGR <65 82FLT1 <65 <65FLT3 <65 <65

FLT3(D835H) <65 <65FLT3(D835Y) <65 <65

FLT3(ITD) <65 <65FLT3(K663Q) <65 <65FLT3(N841I) <65 <65FLT3(R834Q) <65 <65

FLT4 <65 <65FRK <65 <65FYN <65 <65GAK <65 <65

GCN2(Kin.Dom.2,S808G) <65 <65GRK1 <65 <65GRK4 <65 <65GRK7 <65 <65

GSK3A <65 <65GSK3B <65 <65

HCK <65 <65HIPK1 <65 <65HIPK2 <65 <65HIPK3 <65 <65HIPK4 <65 <65HPK1 <65 <65HUNK <65 <65

ICK <65 <65IGF1R <65 <65

IKK-alpha <65 <65IKK-beta <65 <65

IKK-epsilon <65 <65INSR <65 <65

INSRR <65 <65IRAK1 <65 <65IRAK3 <65 <65IRAK4 <65 <65

ITK <65 <65JAK1(JH1domain-catalytic) <65 <65

JAK1(JH2domain-pseudokinase) <65 <65JAK2(JH1domain-catalytic) <65 <65




in KINOMEscan

JAK3(JH1domain-catalytic) <65 <65JNK1 <65 <65JNK2 <65 <65JNK3 <65 <65KIT 92 100

KIT(A829P) <65 <65KIT(D816H) <65 <65KIT(D816V) <65 <65KIT(L576P) 87 99KIT(V559D) 95 100

KIT(V559D,T670I) <65 <65KIT(V559D,V654A) <65 83

LATS1 <65 <65LATS2 <65 <65LCK <65 <65

LIMK1 <65 <65LIMK2 <65 <65LKB1 <65 <65LOK <65 <65

LRRK2 <65 <65LRRK2(G2019S) <65 <65

LTK <65 <65LYN <65 65LZK <65 <65MAK <65 <65

MAP3K1 <65 <65MAP3K15 <65 <65MAP3K2 <65 <65MAP3K3 <65 <65MAP3K4 <65 <65MAP4K2 <65 <65MAP4K3 <65 <65MAP4K4 <65 <65MAP4K5 <65 <65

MAPKAPK2 <65 <65MAPKAPK5 <65 <65

MARK1 <65 <65MARK2 <65 <65MARK3 <65 <65MARK4 <65 <65MAST1 <65 <65MEK1 <65 <65MEK2 <65 <65MEK3 <65 <65MEK4 <65 <65MEK5 <65 70MEK6 <65 <65MELK <65 <65

MERTK <65 <65




in KINOMEscan

MET <65 <65MET(M1250T) <65 <65MET(Y1235D) <65 <65

MINK <65 <65MKK7 <65 <65

MKNK1 <65 <65MKNK2 <65 <65MLCK <65 <65MLK1 <65 <65MLK2 <65 <65MLK3 <65 <65

MRCKA <65 <65MRCKB <65 <65MST1 <65 <65

MST1R <65 <65MST2 <65 <65MST3 <65 <65MST4 <65 <65MTOR <65 <65MUSK <65 <65MYLK <65 <65MYLK2 <65 <65MYLK4 <65 <65MYO3A <65 <65MYO3B <65 <65NDR1 <65 <65NDR2 <65 <65NEK1 <65 <65NEK11 <65 <65NEK2 <65 <65NEK3 <65 <65NEK4 <65 <65NEK5 <65 <65NEK6 <65 <65NEK7 <65 <65NEK9 <65 <65NIM1 <65 <65NLK <65 <65

OSR1 <65 <65p38-alpha <65 <65p38-beta <65 <65p38-delta <65 <65

p38-gamma <65 <65PAK1 <65 <65PAK2 <65 <65PAK3 <65 <65PAK4 <65 <65PAK6 <65 <65PAK7 <65 <65




in KINOMEscan

PCTK1 <65 <65PCTK2 <65 <65PCTK3 <65 <65

PDGFRA 76 99PDGFRB 92 100PDPK1 <65 <65

PFCDPK1(P.falciparum) <65 <65PFPK5(P.falciparum) <65 <65

PFTAIRE2 <65 <65PFTK1 <65 <65PHKG1 <65 <65PHKG2 <65 <65

PIK3C2B <65 <65PIK3C2G <65 <65PIK3CA <65 <65

PIK3CA(C420R) <65 <65PIK3CA(E542K) <65 <65PIK3CA(E545A) <65 <65PIK3CA(E545K) <65 <65PIK3CA(H1047L) <65 <65PIK3CA(H1047Y) <65 <65PIK3CA(I800L) <65 <65

PIK3CA(M1043I) <65 <65PIK3CA(Q546K) <65 <65

PIK3CB <65 <65PIK3CD <65 <65PIK3CG <65 <65PIK4CB <65 <65

PIM1 <65 <65PIM2 <65 <65PIM3 <65 <65

PIP5K1A <65 <65PIP5K1C <65 <65PIP5K2B <65 <65PIP5K2C <65 <65

PKAC-alpha <65 <65PKAC-beta <65 <65PKMYT1 <65 <65

PKN1 <65 <65PKN2 <65 <65

PKNB(M.tuberculosis) <65 <65PLK1 <65 <65PLK2 <65 <65PLK3 <65 <65PLK4 <65 <65

PRKCD <65 <65PRKCE <65 <65PRKCH <65 <65PRKCI <65 <65




in KINOMEscan

PRKCQ <65 <65PRKD1 <65 <65PRKD2 <65 <65PRKD3 <65 <65PRKG1 <65 <65PRKG2 <65 <65PRKR <65 <65PRKX <65 <65PRP4 <65 <65PYK2 <65 <65QSK <65 <65RAF1 <65 <65RET <65 91

RET(M918T) <65 94RET(V804L) <65 <65RET(V804M) <65 <65

RIOK1 <65 <65RIOK2 <65 <65RIOK3 <65 <65RIPK1 <65 <65RIPK2 <65 <65RIPK4 <65 <65RIPK5 <65 <65

ROCK1 <65 <65ROCK2 <65 <65ROS1 <65 <65

RPS6KA4(Kin.Dom.1-N-terminal) <65 <65RPS6KA4(Kin.Dom.2-C-terminal) <65 <65RPS6KA5(Kin.Dom.1-N-terminal) <65 <65RPS6KA5(Kin.Dom.2-C-terminal) <65 <65

RSK1(Kin.Dom.1-N-terminal) <65 <65RSK1(Kin.Dom.2-C-terminal) <65 <65RSK2(Kin.Dom.1-N-terminal) <65 <65RSK3(Kin.Dom.1-N-terminal) <65 <65RSK3(Kin.Dom.2-C-terminal) <65 <65RSK4(Kin.Dom.1-N-terminal) <65 <65RSK4(Kin.Dom.2-C-terminal) <65 <65

S6K1 <65 <65SBK1 <65 <65

SgK110 <65 <65SGK3 <65 <65SIK <65 <65

SIK2 <65 <65SLK <65 <65

SNARK <65 <65SNRK <65 <65SRC <65 <65

SRMS <65 <65SRPK1 <65 <65




in KINOMEscan

SRPK2 <65 <65SRPK3 <65 <65STK16 <65 <65STK33 <65 <65STK35 <65 <65STK36 <65 <65STK39 <65 <65SYK <65 <65TAK1 <65 <65

TAOK1 <65 <65TAOK2 <65 <65TAOK3 <65 <65TBK1 <65 <65TEC <65 <65

TESK1 <65 <65TGFBR1 <65 <65TGFBR2 <65 <65

TIE1 <65 <65TIE2 <65 <65TLK1 <65 <65TLK2 <65 <65TNIK <65 <65TNK1 <65 <65TNK2 <65 <65

TNNI3K <65 <65TRKA <65 <65TRKB <65 <65TRKC <65 <65

TRPM6 <65 <65TSSK1B <65 <65

TTK <65 <65TXK <65 <65

TYK2(JH1domain-catalytic) <65 <65TYK2(JH2domain-pseudokinase) <65 <65

TYRO3 <65 <65ULK1 <65 <65ULK2 <65 <65ULK3 <65 <65

VEGFR2 <65 <65VRK2 <65 <65WEE1 <65 <65WEE2 <65 <65YANK1 <65 <65YANK2 <65 <65YANK3 <65 <65

YES <65 <65YSK1 <65 <65YSK4 <65 <65ZAK <65 <65

ZAP70 <65 <65


Supplementary Table S3Selective antiproliferative activity of CH5183284/Debio 1347 against cancer cell lines harboring genetic alterations in FGFR

Cell line Tumor typeCH5183284 IC50 (µM)

FGFR genetic alterations

SNU-16 Gastric cancer 0.017 FGFR2 gene amplificationKato-III Gastric cancer 0.018 FGFR2 gene amplificationHSC-39 Gastric cancer 0.050 FGFR2 gene amplification

AGS Gastric cancer 2.9HGC-27 Gastric cancer 3.0 MKN-1 Gastric cancer 3.0 MKN-45 Gastric cancer 5.0 SNU-1 Gastric cancer 5.0 JR-St Gastric cancer 7.1

NCI-N87 Gastric cancer 10NUGC-4 Gastric cancer >10MKN-74 Gastric cancer >10NUGC-3 Gastric cancer >10

SCH Gastric cancer >10MKN-28 Gastric cancer >10SNU-5 Gastric cancer >10

MFE-296 Endometrial cancer 0.042 FGFR2 N549K mutationAN3 CA Endometrial cancer 0.054 FGFR2 K310R/N549K mutationMFE-280 Endometrial cancer 0.41 FGFR2 S252W mutationHEC-59 Endometrial cancer 2.8HEC-1-B Endometrial cancer 5.7HEC-1-A Endometrial cancer 9.2

KLE Endometrial cancer 10HEC-151 Endometrial cancer 10RL95-2 Endometrial cancer >10

HEC-50B Endometrial cancer >10HEC-108 Endometrial cancer >10RT112/84 Bladder cancer 0.018 FGFR3-TACC3 fusionUM-UC-14 Bladder cancer 0.11 FGFR3 S249C mutation

SW780 Bladder cancer 0.12 FGFR3-BAIAP2L1 fusionRT4 Bladder cancer 0.35 FGFR3-TACC3 fusionT24 Bladder cancer 2.65637 Bladder cancer 3.5J82 Bladder cancer 4.1

SCaBER Bladder cancer 5.8 JMSU1 Bladder cancer 7.1

UM-UC-3 Bladder cancer 7.2HT-1376 Bladder cancer 10HT-1197 Bladder cancer >10TCCSUP Bladder cancer >10BFTC-905 Bladder cancer >10

647-V Bladder cancer >10KMS-11 Multiple Myeloma 0.14 FGFR3 Y373C mutationOPM-2 Multiple Myeloma 1.3

KMS-12-PE Multiple Myeloma 2.7 KMS-26 Multiple Myeloma 3.0

KMS-21BM Multiple Myeloma 4.5 FGFR3 K650E mutationNCI-H929 Multiple Myeloma 5.6

IM-9 Multiple Myeloma 6.0 FGFR3 F386L mutationKMS-34 Multiple Myeloma 7.7




KMM-1 Multiple Myeloma 8.6 KMS-12-BM Multiple Myeloma >10

KHM-1B Multiple Myeloma >10LP-1 Multiple Myeloma >10

KMS-20 Multiple Myeloma >10L-363 Multiple Myeloma >10

KMS-28BM Multiple Myeloma >10NCI-H520 Non-small cell lung cancer, Squamouse 0.30 FGFR1 gene amplification

PC-1 Non-small cell lung cancer, Squamouse 1.3HARA Non-small cell lung cancer, Squamouse 9.1

HARA-B Non-small cell lung cancer, Squamouse 9.8NCI-H226 Non-small cell lung cancer, Squamouse >10

QG-56 Non-small cell lung cancer, Squamouse >10NCI-H2170 Non-small cell lung cancer, Squamouse >10

Calu-1 Non-small cell lung cancer, Squamouse >10PC-10 Non-small cell lung cancer, Squamouse >10 FGFR2 V12M mutation

SK-MES-1 Non-small cell lung cancer, Squamouse >10NCI-H1703 Non-small cell lung cancer, Adenocarcinoma 0.79 FGFR1 gene amplification

PC-9 Non-small cell lung cancer, Adenocarcinoma 2.8HCC78 Non-small cell lung cancer, Adenocarcinoma 5.0ABC-1 Non-small cell lung cancer, Adenocarcinoma 5.5

NCI-H1395 Non-small cell lung cancer, Adenocarcinoma 5.9NCI-H23 Non-small cell lung cancer, Adenocarcinoma 6.0

NCI-H2009 Non-small cell lung cancer, Adenocarcinoma 6.8NCI-H1755 Non-small cell lung cancer, Adenocarcinoma 8.0NCI-H1568 Non-small cell lung cancer, Adenocarcinoma 9.2NCI-H2122 Non-small cell lung cancer, Adenocarcinoma >10NCI-H838 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1355 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1944 Non-small cell lung cancer, Adenocarcinoma >10COR-L105 Non-small cell lung cancer, Adenocarcinoma >10SK-LU-1 Non-small cell lung cancer, Adenocarcinoma >10

NCI-H1437 Non-small cell lung cancer, Adenocarcinoma >10HCC827 Non-small cell lung cancer, Adenocarcinoma >10

NCI-H2347 Non-small cell lung cancer, Adenocarcinoma >10NCI-H522 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1993 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1792 Non-small cell lung cancer, Adenocarcinoma >10

A549 Non-small cell lung cancer, Adenocarcinoma >10NCI-H2023 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1975 Non-small cell lung cancer, Adenocarcinoma >10NCI-H2228 Non-small cell lung cancer, Adenocarcinoma >10

Calu-3 Non-small cell lung cancer, Adenocarcinoma >10NCI-H2030 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1838 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1793 Non-small cell lung cancer, Adenocarcinoma >10NCI-H1581 Non-small cell lung cancer, Large cell 0.22 FGFR1 gene amplificationNCI-H292 Non-small cell lung cancer, Mucoepidermoid 1.9NCI-H1155 Non-small cell lung cancer, Large cell 2.1NCI-H1666 Non-small cell lung cancer, Bronchiolo-Alveolar 5.3




NCI-H596 Non-small cell lung cancer, Adenosquamous 6.1NCI-H2110 Non-small cell lung cancer 6.9

Calu-6 Non-small cell lung cancer 8.2NCI-H661 Non-small cell lung cancer, Large cell 8.6NCI-H460 Non-small cell lung cancer, Large cell 8.9NCI-H441 Non-small cell lung cancer, Papillary >10HCC366 Non-small cell lung cancer, Adenosquamous >10PC-13 Non-small cell lung cancer, Large cell >10

NCI-H1299 Non-small cell lung cancer, Large cell >10NCI-H1650 Non-small cell lung cancer, Bronchiolo-Alveolar >10NCI-H1781 Non-small cell lung cancer, Bronchiolo-Alveolar >10LCLC-103H Non-small cell lung cancer, Large cell >10

DMS 114 Small cell lung cancer 0.18 FGFR1 gene amplificationNCI-H2227 Small cell lung cancer 1.4 NCI-H82 Small cell lung cancer 2.6SHP-77 Small cell lung cancer 5.6

NCI-H526 Small cell lung cancer 8.7NCI-H1930 Small cell lung cancer >10

DMS 53 Small cell lung cancer >10SUM-52PE Breast cancer 0.018 FGFR2 gene amplificationMFM-223 Breast cancer 0.058 FGFR2 gene amplificationHCC2218 Breast cancer 1.2

MCF10DCIS.com Breast cancer 1.6MDA-MB-157 Breast cancer 2.3

DU-4475 Breast cancer 3.1Hs 578.T Breast cancer 3.7MCF10A Breast normal 6.2HCC38 Breast cancer 6.4

SUM-44PE Breast cancer 6.9 FGFR1 gene amplificationSUM-229PE Breast cancer 7.4MDA-MB-453 Breast cancer 7.7MDA-MB-468 Breast cancer 8.0

MCF7 Breast cancer 8.4HCC1500 Breast cancer 8.6HCC1187 Breast cancer 9.2

MDA-MB-175-VII Breast cancer >10CAL-120 Breast cancer >10 FGFR1 gene amplificationHCC1569 Breast cancer >10HCC1599 Breast cancer >10ZR-75-1 Breast cancer >10 FGFR1 gene amplification

MDA-MB-231 Breast cancer >10JIMT-1 Breast cancer >10 FGFR1 gene amplification

CAMA-1 Breast cancer >10 FGFR1 gene amplificationHCC1395 Breast cancer >10 FGFR1 S125L mutation

BT-474 Breast cancer >10HCC1806 Breast cancer >10HCC70 Breast cancer >10

HCC1954 Breast cancer >10T47D Breast cancer >10

HCC1419 Breast cancer >10




ZR-75-30 Breast cancer >10HCC1937 Breast cancer >10SK-BR-3 Breast cancer >10HCC1428 Breast cancer >10COLO-824 Breast cancer >10UACC-812 Breast cancer >10HCC1143 Breast cancer >10

MDA-MB-361 Breast cancer >10BT-20 Breast cancer >10

MDA-MB-134-VI Breast cancer >10 FGFR1 gene amplificationBT-483 Breast cancer >10

NCI-H716 Colorectal cancer 0.013 FGFR2 gene amplificationCOLO-205 Colorectal cancer 2.9

HCT-8 Colorectal cancer 3.2CaR-1 Colorectal cancer 5.8SW48 Colorectal cancer 5.9

LS174T Colorectal cancer 7.5LS513 Colorectal cancer 7.9HT-29 Colorectal cancer 7.9

COLO-201 Colorectal cancer 7.9NCI-H508 Colorectal cancer 8.3

SW620 Colorectal cancer 8.3RKO Colorectal cancer 8.7

SW480 Colorectal cancer 8.8LS411N Colorectal cancer 9.0 HCT-116 Colorectal cancer 10LS1034 Colorectal cancer >10HCT-15 Colorectal cancer >10

WiDr Colorectal cancer >10CW-2 Colorectal cancer >10T84 Colorectal cancer >10

SW948 Colorectal cancer >10SW1417 Colorectal cancer >10DLD-1 Colorectal cancer >10

SW1463 Colorectal cancer >10LoVo Colorectal cancer >10

SW403 Colorectal cancer >10Caco-2 Colorectal cancer >10

COLO-320DM Colorectal cancer >10SW1116 Colorectal cancer >10

KG-1 Leukemia, Myeloid, Acute 0.014 FGFR1OP-FGFR1 fusionKG-1a Leukemia, Myeloid, Acute 0.030 FGFR1OP-FGFR1 fusion

MV-4-11 Leukemia, Biphenotypic, Acute 1.9NB-4 Leukemia, Promyelocytic, Acute 2.110C9 Lymphoma, Non-Hodgkin 2.3

MOLM-13 Leukemia, Myeloid, Acute 2.5Raji Burkitt Lymphoma 3.1

Ramos Burkitt Lymphoma 3.5MEG-01 Leukemia, Myelogenous, Chronic 4.1MC/CAR Plasmacytoma 4.1




KARPAS-299 Lymphoma, Large-Cell, Anaplastic 4.1U-698-M Lymphoma, B-Cell 4.4

K-562 Leukemia, Myelogenous, Chronic 5.0 CMK-11-5 Leukemia, Megakaryoblastic, Acute 5.1ARH-77 Leukemia 5.6NKM-1 Leukemia, Myeloid, Acute 5.7U-937 Lymphoma, Large B-Cell, Diffuse 6.1

SR Lymphoma, Large-Cell, Immunoblastic 6.2SU-DHL-1 Lymphoma, Large-Cell, Anaplastic >10

HEL Leukemia, Erythroblastic, Acute >10U266B1 Plasmacytoma >10CEM/C2 Leukemia, T-Cell >10TF-1a Leukemia, Erythroblastic, Acute >10

CCRF-CEM Leukemia >10RPMI-8226 Plasmacytoma >10NOMO-1 Leukemia, Myeloid, Acute >10

HL-60 Leukemia, Promyelocytic, Acute >10HDLM-2 Lymph Nodes >10F-36P Leukemia, Myeloid, Acute >10THP-1 Leukemia, Monocytic, Acute >10SKM-1 Leukemia, Myeloid, Acute >10HMCB Melanoma 0.94

SK-MEL-5 Melanoma 3.0 A2058 Melanoma 4.1A-375 Melanoma 5.4 FGFR2 E636K mutation

SK-MEL-30 Melanoma 5.5SK-MEL-1 Melanoma 8.9

SK-MEL-28 Melanoma >10MDA-MB-435S Melanoma >10

MeWo Melanoma >10A-431 Skin cancer, Squamous Cell >10

SK-MEL-2 Melanoma >10C32 Melanoma >10

HuH-7 Liver cancer 3.0 HuH-1 Liver cancer 5.3HepG2 Liver cancer >10

PLC/PRF/5 Liver cancer >10Hep3B Liver cancer >10

SK-HEP-1 Liver cancer >10HLE Liver cancer >10

Hs 38.T Ovarian cancer 2.3OVMANA Ovarian cancer 2.7

RMG-I Ovarian cancer 5.9ES2 Ovarian cancer 6.2PA-1 Ovarian cancer 9.5

COLO-704 Ovarian cancer >10SW626 Ovarian cancer >10

SK-OV-3 Ovarian cancer >10OVCAR-3 Ovarian cancer >10

MCAS Ovarian cancer >10




EFO-21 Ovarian cancer >10HPAC Pancreas cancer 1.4KP-4 Pancreas cancer 5.5YAPC Pancreas cancer 5.9

Mia PaCa-2 Pancreas cancer 7.7Panc-1 Pancreas cancer >10BxPC-3 Pancreas cancer >10HuP-T4 Pancreas cancer >10

SU.86.86 Pancreas cancer >10Capan-1 Pancreas cancer >10HPAF-II Pancreas cancer >10

CFPAC-1 Pancreas cancer >10Capan-2 Pancreas cancer >10AsPC-1 Pancreas cancer >10

Hs 766.T Pancreas cancer >10A-172 Glioblastoma 0.31NCCIT Teratocarcinoma 0.44SW579 Thyroid cancer 0.85U-2197 Histiocytoma 1.1

NTERA-2 Teratocarcinoma 1.1CCF-STTG1 Astrocytoma 1.2KYSE-150 Esophageal cancer 1.3D-341MED Medulloblastoma 1.6

NB-1 Neuroblastoma 1.8HT-1080 Fibrosarcoma 1.8C-33 A Cervix cancer 2.0

COLO-684 Uterus cancer 2.0 IMR-32 Neuroblastoma 2.2

KYSE-70 Esophageal cancer 2.3TT Thyroid cancer 2.9

143B Osteosarcoma 2.9SK-N-DZ Neuroblastoma 3.7

RPMI-2650 Nasal cancer 3.8SH-SY5Y Neuroblastoma 4.0

Ca Ski Cervix cancer 4.2SJCRH30 Rhabdomyosarcoma 4.3

SCC-9 Tongue cancer 4.4T98G Glioblastoma 4.5Daoy Medulloblastoma 5.5786-O Renal cancer 6.0

D-283MED Medulloblastoma 6.1OE19 Esophageal cancer 6.4

NCI-H358 Bronchial cancer 6.6EGI-1 Cholangiocarcinoma 8.1

KYSE-520 Esophageal cancer 8.3U-138 MG Glioblastoma 9.8SK-N-SH Neuroblastoma 9.8

LN-18 Glioblastoma 9.9SK-N-F1 Neuroblastoma 9.9RH-30 Rhabdomyosarcoma 10




SK-ES-1 Ewing sarcoma 10Detroit 562 Pharynx cancer >10

CAL-27 Tongue cancer >10NCI-H28 Mesothelioma >10SK-N-AS Neuroblastoma >10KELLY Neuroblastoma >10HuH-28 Cholangiocarcinoma >10ACHN Renal cancer >10Caki-1 Renal cancer >10A-204 Rhabdomyosarcoma >10

ME-180 Cervix cancer >10SNG-M Uterus cancer >10SCC-25 Tongue cancer >10A-673 Rhabdomyosarcoma >10PC-3 Prostate cancer >10

SCC-15 Tongue cancer >10SCC-4 Tongue cancer >1022Rv1 Prostate cancer >10

U-118 MG Glioblastoma >108305C Thyroid cancer >10DU-145 Prostate cancer >10

U-87 MG Glioblastoma >10VCaP Prostate cancer >10MG-63 Osteosarcoma >10

Y79 Retinoblastoma >10RB247c Retinoblastoma >10

WERI-Rb-1 Retinoblastoma >10


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Supplementary Figure S1