Drug Information

Drug (ID: DG01612) and It's Reported Resistant Information
Name
DEBIO-1347
Synonyms
1265229-25-1; CH5183284; Debio-1347; zoligratinib; CH-5183284; CH5183284 (Debio-1347); Debio 1347; UNII-NR9ZYH80Z8; FF284; NR9ZYH80Z8; CHEMBL3907479; (5-Amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone; [5-Amino-1-(2-Methyl-1h-Benzimidazol-6-Yl)-1h-Pyrazol-4-Yl](1h-Indol-2-Yl)methanone; [5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone; Fgfr inhibitor debio 1347; DEBIO1347; GTPL9787; SCHEMBL10002991; HMS3674G21; HMS3748K13; BCP14354; EX-A1122; BDBM50197683; MFCD28502053; NSC782363; NSC800074; s7665; ZINC98209140; AKOS027427006; CH5183284; Debio-1347; CCG-264725; CS-5504; DB12903; NSC-782363; NSC-800074; SB16908; Methanone, (5-amino-1-(2-methyl-1H-benzimidazol-6-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl-; NCGC00386433-01; AC-32960; BS-14797; HY-19957; CH 5183284; J3.616.632K; A14415; A901067; Q27285013; (5-amino-1-(2-methyl-3H-benzo[d]imidazol-5-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone; [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(1H-indol-2-yl) methanone; [5-Amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(1H-indol-2-yl)-methanone; [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(1H-indol-2-yl)methanone; [5-amino-1-(2-methyl-3h-benzimidazol-5-yl)pyrazol-4-yl](1h-indol-2-yl)methanone; 1-(2-Methyl-1H-benzoimidazole-6-yl)-4-(1H-indole-2-ylcarbonyl)-1H-pyrazole-5-amine; LWJ
    Click to Show/Hide
Indication
In total 1 Indication(s)
Discovery agent [ICD-11: N.A.]
Phase 2
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target Enhancer of zeste homolog 2 (EZH2) EZH2_HUMAN [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
3
IsoSMILES
CC1=NC2=C(N1)C=C(C=C2)N3C(=C(C=N3)C(=O)C4=CC5=CC=CC=C5N4)N
InChI
InChI=1S/C20H16N6O/c1-11-23-16-7-6-13(9-17(16)24-11)26-20(21)14(10-22-26)19(27)18-8-12-4-2-3-5-15(12)25-18/h2-10,25H,21H2,1H3,(H,23,24)
InChIKey
BEMNJULZEQTDJY-UHFFFAOYSA-N
PubChem CID
66555680
TTD Drug ID
D02BBA
DrugBank ID
DB12903
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
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) [1]
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
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G
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470
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480
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G
C
C
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G
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490
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E
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G
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500
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510
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520
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M
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E
M
M
M
M
530
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K
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M
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I
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G
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H
K
K
N
N
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I
540
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N
L
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G
A
A
C
C
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G
G
G
550
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L
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E
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A
A
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560
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K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
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R
A
A
570
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R
R
R
R
P
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G
G
-
L
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D
-
Y
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F
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580
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D
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T
-
C
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K
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P
-
E
E
E
E
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Q
L
L
590
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T
T
F
F
K
K
D
D
L
L
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V
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S
C
C
A
A
Y
Y
600
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Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
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L
L
A
A
610
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S
S
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K
K
C
C
I
I
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H
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R
D
D
L
L
A
A
620
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A
A
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R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
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V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
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R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
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K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
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K
660
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W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
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V
V
Y
Y
T
T
H
H
Q
Q
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D
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V
W
W
S
S
680
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F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
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L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
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V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
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G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
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T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
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C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
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740
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T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
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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 DEBIO-1347 by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V564I (c.1690G>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V564L (c.1690G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
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 DEBIO-1347 by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
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 DEBIO-1347 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 3 (FGFR3) [1]
Sensitive 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
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M
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440
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H
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H
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Q
G
D
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P
450
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M
T
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L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
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P
P
E
A
D
D
P
P
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K
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W
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E
F
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470
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D
A
K
R
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L
T
T
L
L
G
G
K
K
P
P
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L
G
G
480
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E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
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E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
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A
A
K
K
P
P
V
V
T
T
V
V
A
A
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V
K
K
M
M
510
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L
L
K
K
D
D
D
D
A
A
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T
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D
K
K
D
D
L
L
520
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S
D
D
L
L
V
V
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E
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M
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E
M
M
M
M
530
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K
K
M
M
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G
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H
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K
N
N
I
I
I
I
540
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N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
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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
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D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
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Q
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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
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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
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L
P
P
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V
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660
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W
W
M
M
A
A
P
P
E
E
A
A
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L
F
F
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D
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R
670
|
V
V
Y
Y
T
T
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H
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Q
S
S
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D
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W
W
S
S
680
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F
F
G
G
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L
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L
L
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E
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I
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690
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L
L
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G
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G
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P
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Y
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G
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700
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V
E
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E
E
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E
710
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G
G
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P
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A
N
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C
C
720
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T
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D
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L
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Y
M
M
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I
M
M
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E
730
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C
C
W
W
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H
A
A
A
A
P
P
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Q
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P
P
740
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T
T
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F
K
K
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Q
L
L
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V
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E
D
D
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L
D
D
750
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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 sensitivity of DEBIO-1347 by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Sensitive 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
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M
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400
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440
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460
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P
470
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E
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480
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E
490
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G
C
C
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F
G
G
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Q
V
V
V
V
M
M
A
A
E
E
500
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A
A
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G
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I
D
D
K
K
D
D
K
K
P
P
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K
510
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E
E
A
A
V
V
T
T
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A
A
V
V
K
K
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L
520
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K
K
D
D
D
D
A
A
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T
E
E
K
K
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D
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530
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D
D
L
L
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V
S
S
E
E
M
M
E
E
M
M
M
M
K
K
540
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M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
N
N
550
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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 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Myeloproliferative neoplasm [ICD-11: 2A22]
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) [2]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 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
-
G
-
S
-
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 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y373C (c.1118A>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 Disease Info 
Molecule Alteration Missense mutation
p.F386L (c.1156T>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Endometrial cancer [ICD-11: 2C76]
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 2 (FGFR2) [2]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
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) [2]
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
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]
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
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [4]
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) [4]
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) [4]
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) [3]
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) [3]
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) [4]
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
References
Ref 1 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 2 The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitorMol Cancer Ther. 2014 Nov;13(11):2547-58. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28.
Ref 3 Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivoBr J Cancer. 2011 Jan 4;104(1):75-82. doi: 10.1038/sj.bjc.6606016. Epub 2010 Nov 30.
Ref 4 A Phase I, Open-Label, Multicenter, Dose-escalation Study of the Oral Selective FGFR Inhibitor Debio 1347 in Patients with Advanced Solid Tumors Harboring FGFR Gene AlterationsClin Cancer Res. 2019 May 1;25(9):2699-2707. doi: 10.1158/1078-0432.CCR-18-1959. Epub 2019 Feb 11.

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