Drug Information

Drug (ID: DG00550) and It's Reported Resistant Information
Name
Infigratinib
Synonyms
NVP-BGJ398; Infigratinib; 872511-34-7; BGJ398; BGJ-398; BGJ 398; Infigratinib free base; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea; UNII-A4055ME1VK; BGJ398 (NVP-BGJ398); MVP-BGJ398; A4055ME1VK; CHEBI:63451; 872511-34-7 (free base); 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)-1-methylurea; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)phenylamino)pyrimidin-4-yl)-1-methylurea; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea; C26H31Cl2N7O3; Truseltiq; CHEMBL1834657; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea.; 3-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-[6-[[4-(4-ethylpiperazin-1-yl)phenyl]amino]pyrimidin-4-yl]-1-methylurea; Infigratinib [INN]; Infigratinib [USAN]; Infigratinib (BGJ398); Infigratinib (USAN/INN); Infigratinib [USAN:INN]; NVP-BGJ389; NVP-BGJ398(Infigratinib); MLS006010953; SCHEMBL374435; GTPL7877; QCR-48; CHEMBL1852688; DTXSID70236238; EX-A057; SYN1152; BGJ398, BGJ-398; HMS3295O21; AMY10737; AOB87703; BCP03602; BGJ398 - NVP-BGJ398; BDBM50355393; FD5035; MFCD22123241; NSC764487; s2183; WHO 10032; ZINC72105034; AKOS025149513; AKOS032949944; BCP9000399; CS-0586; DB11886; NSC-764487; SB16612; NCGC00274030-01; NCGC00274030-11; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)-phenylamino)pyrimidin-4-yl)-1-methylurea; AC-28417; AS-16290; HY-13311; SMR004702757; Urea, N'-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(6-((4-(4-ethyl-1-piperazinyl)phenyl)amino)-4-pyrimidinyl)-N-methyl-; BCP0726000187; FT-0699366; Y0313; D11589; J-510477; BRD-K42728290-001-01-8; Q27075200; 07J; 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea
    Click to Show/Hide
Indication
In total 2 Indication(s)
Cholangiocarcinoma [ICD-11: 2C12]
Approved
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (4 diseases)
Head and neck cancer [ICD-11: 2D42]
[2]
Liver cancer [ICD-11: 2C12]
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[3]
Transitional cell carcinoma [ICD-11: 2C9Z]
[4]
Target Fibroblast growth factor receptor (FGFR) NOUNIPROTAC [1]
Fibroblast growth factor receptor 1 (FGFR1) FGFR1_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C26H31Cl2N7O3
IsoSMILES
CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl
InChI
1S/C26H31Cl2N7O3/c1-5-34-10-12-35(13-11-34)18-8-6-17(7-9-18)31-21-15-22(30-16-29-21)33(2)26(36)32-25-23(27)19(37-3)14-20(38-4)24(25)28/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31)
InChIKey
QADPYRIHXKWUSV-UHFFFAOYSA-N
PubChem CID
53235510
ChEBI ID
CHEBI:63451
TTD Drug ID
D03LWG
DrugBank ID
DB11886
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
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G
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S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V564F (c.1690G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 2PSQ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.22  Å
PDB: 7KIA
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.64
TM score: 0.98452
Amino acid change:
V564F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
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400
|
G
-
S
-
S
-
H
-
H
-
H
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H
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H
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H
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S
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410
|
Q
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D
-
P
-
P
-
A
-
V
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H
-
K
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L
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T
-
420
|
K
-
R
-
I
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P
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L
-
R
-
R
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Q
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V
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T
-
430
|
V
-
S
-
A
-
E
-
S
-
S
-
S
-
S
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M
-
N
-
440
|
S
-
N
-
T
-
P
-
L
-
V
-
R
-
I
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T
-
T
-
450
|
R
-
L
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S
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S
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T
-
A
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D
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T
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P
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M
-
460
|
L
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A
A
G
G
V
V
S
S
E
E
Y
Y
E
E
L
L
P
P
470
|
E
E
D
D
P
P
K
K
W
W
E
E
F
F
P
P
R
R
D
D
480
|
K
K
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
E
E
490
|
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
E
E
500
|
A
A
V
V
G
G
I
I
D
D
K
K
D
D
K
K
P
P
K
K
510
|
E
E
A
A
V
V
T
T
V
V
A
A
V
V
K
K
M
M
L
L
520
|
K
K
D
D
D
D
A
A
T
T
E
E
K
K
D
D
L
L
S
S
530
|
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
K
K
540
|
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
N
N
550
|
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
D
D
G
G
P
P
560
|
L
L
Y
Y
V
V
I
I
V
F
E
E
Y
Y
A
A
S
S
K
K
570
|
G
G
N
N
L
L
R
R
E
E
Y
Y
L
L
R
R
A
A
R
R
580
|
R
R
P
P
P
P
G
G
M
M
E
E
Y
Y
S
S
Y
Y
D
D
590
|
I
I
N
N
R
R
V
V
P
P
E
E
E
E
Q
Q
M
M
T
T
600
|
F
F
K
K
D
D
L
L
V
V
S
S
C
C
T
T
Y
Y
Q
Q
610
|
L
L
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
S
S
620
|
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
A
A
630
|
R
R
N
N
V
V
L
L
V
V
T
T
E
E
N
N
N
N
V
V
640
|
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
R
R
650
|
D
D
I
I
N
N
N
N
I
I
D
D
Y
Y
Y
Y
K
K
K
K
660
|
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
W
W
670
|
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
V
V
680
|
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
F
F
690
|
G
G
V
V
L
L
M
M
W
W
E
E
I
I
F
F
T
T
L
L
700
|
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
V
V
710
|
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
G
G
720
|
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
T
T
730
|
N
N
E
E
L
L
Y
Y
M
M
M
M
M
M
R
R
D
D
C
C
740
|
W
W
H
H
A
A
V
V
P
P
S
S
Q
Q
R
R
P
P
T
T
750
|
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
R
R
760
|
I
I
L
L
T
T
L
L
T
T
T
T
N
N
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.V564F (c.1690G>T) in gene FGFR2 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.N540K (c.1620C>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V555L (c.1663G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.V555L (c.1663G>C) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L608V (c.1822T>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K660E (c.1978A>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K660N (c.1980G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.W290C (c.870G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R248C (c.742C>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.R248C (c.742C>T) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.S249C (c.746C>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Duplication
p.S267_D273 (c.799_819)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Complex-indel
p.W290_I291delinsC (c.870_872delGAT)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Liver cancer [ICD-11: 2C12]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 1 (FGFR1) [1]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
 Disease Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MET signalling pathway Activation hsa04020
ERK/MAPK signaling pathway Activation hsa04210
In Vitro Model DMS114 cells Lung Homo sapiens (Human) CVCL_1174
Mechanism Description Upregulation of the MET signalling pathway leading to re-activation of the ERK/MAPK pathway was observed in conjunction with the development of resistance to infigratinib in FGFR1-amplified DMS114 lung cancer cells.
Key Molecule: Fibroblast growth factor receptor 1 (FGFR1) [1]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
 Disease Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MET signalling pathway Activation hsa04020
ERK/MAPK signaling pathway Activation hsa04210
In Vitro Model DMS114 cells Lung Homo sapiens (Human) CVCL_1174
Mechanism Description Upregulation of the MET signalling pathway leading to re-activation of the ERK/MAPK pathway was observed in conjunction with the development of resistance to infigratinib in FGFR1-amplified DMS114 lung cancer cells.
Bladder cancer [ICD-11: 2C94]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [7]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G370C (c.1108G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [7]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y373C (c.1118A>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [7]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R248C (c.742C>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [8]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S371C (c.1111A>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [8]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G380R (c.1138G>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [7]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S249C (c.746C>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [8]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Synonymous
p.K650K (c.1950G>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Urinary system cancer [ICD-11: 2C95]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [9]
Sensitive Disease Urinary system cancer [ICD-11: 2C95.Y]
 Disease Info 
Molecule Alteration Missense mutation
p.S249C (c.746C>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
KG-1 cells Bone marrow Homo sapiens (Human) CVCL_0374
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
UMUC14 cells Kidney Homo sapiens (Human) CVCL_2747
SNU16 cells Ascites Homo sapiens (Human) CVCL_0076
OPM2 cells Peripheral blood Homo sapiens (Human) CVCL_1625
NCI-H2444 cells Lung Homo sapiens (Human) CVCL_1552
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFM-223 cells Pleural effusion Homo sapiens (Human) CVCL_1408
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Mechanism Description c-Myc functioned as the key downstream effector that preceded FGFR-MEK/ERK signaling in FGFR aberrant cancer. Disruption of c-Myc overrode the cell proliferation driven by constitutively active FGFR. FGFR inhibition in FGFR-addicted cancer facilitated c-Myc degradation via phosphorylating c-Myc at threonine 58. Ectopic expression of undegradable c-Myc mutant conferred resistance to FGFR inhibition both in vitro and in vivo. c-Myc level alteration stringently determined the response to FGFR inhibitors, as demonstrated in FGFR-responsive cancer subset, as well as cancers bearing acquired or de novo resistance to FGFR inhibition.
Transitional cell carcinoma [ICD-11: 2C9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [4]
Resistant Disease Transitional cell carcinoma [ICD-11: 2C9Z.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Head and neck cancer [ICD-11: 2D42]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]
Resistant Disease Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
 Disease Info 
Molecule Alteration Missense mutation
p.S131L (c.392C>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SCC25 cells Oral Homo sapiens (Human) CVCL_1682
HSC3 cells Tongue Homo sapiens (Human) CVCL_1288
FaDu cells Pharynx Homo sapiens (Human) CVCL_1218
HN cells Cervical lymph node Homo sapiens (Human) CVCL_1283
Detroit 562 cells Pleural effusion Homo sapiens (Human) CVCL_1171
584-A2 cells Larynx Homo sapiens (Human) CVCL_V278
Experiment for
Molecule Alteration		 Immunohistochemical staining assay; qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description In vitro, FGFR3 overexpression led to increased proliferation, whereas migration was not altered. Moreover, FGFR3-overexpressing cells were more sensitive to BGJ398. Cells overexpressing FGFR3 mutant versions showed increased proliferation compared to wild-type FGFR3 under serum-reduced conditions and were largely as sensitive as the wild-type protein to BGJ398.
References
Ref 1 Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance .Br J Cancer. 2021 Mar;124(5):880-892. doi: 10.1038/s41416-020-01157-0. Epub 2020 Dec 3. 10.1038/s41416-020-01157-0
Ref 2 Evaluation of FGFR3 as a Therapeutic Target in Head and Neck Squamous Cell CarcinomaTarget Oncol. 2016 Oct;11(5):631-642. doi: 10.1007/s11523-016-0431-z.
Ref 3 Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive CholangiocarcinomaCancer Discov. 2017 Mar;7(3):252-263. doi: 10.1158/2159-8290.CD-16-1000. Epub 2016 Dec 29.
Ref 4 Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 AlterationsCancer Discov. 2018 Jul;8(7):812-821. doi: 10.1158/2159-8290.CD-18-0229. Epub 2018 May 30.
Ref 5 Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinomaCancer Res. 2013 Aug 15;73(16):5195-205. doi: 10.1158/0008-5472.CAN-12-3950. Epub 2013 Jun 20.
Ref 6 Identification of Oncogenic and Drug-Sensitizing Mutations in the Extracellular Domain of FGFR2Cancer Res. 2015 Aug 1;75(15):3139-46. doi: 10.1158/0008-5472.CAN-14-3771. Epub 2015 Jun 5.
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