Drug Information

Drug (ID: DG01594) and It's Reported Resistant Information
Name
AZD-4547
Synonyms
AZD4547; 1035270-39-3; AZD-4547; AZD 4547; UNII-2167OG1EKJ; N-(5-(3,5-dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzamide; 2167OG1EKJ; CHEBI:63453; rel-N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]benzamide; N-{3-[2-(3,5-Dimethoxyphenyl)ethyl]-1h-Pyrazol-5-Yl}-4-[(3r,5s)-3,5-Dimethylpiperazin-1-Yl]benzamide; N-{5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl}-4-(cis-3,5-dimethylpiperazin-1-yl)benzamide; N-{5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl}-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide; 66T; KB-74810; N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide; SCHEMBL63884; N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-rel-3,5-dimethylpiperazin-1-yl)benzamide; GTPL7707; QCR-89; SCHEMBL15250892; DTXSID80145887; AMY16612; AOB87745; EX-A1578; 2240AH; MFCD22580423; NSC764239; NSC765338; NSC799346; s2801; ZINC95616598; AKOS024464898; BCP9000364; CCG-269382; CS-0971; DB12247; NSC-764239; NSC-765338; NSC-799346; NCGC00346713-01; NCGC00346713-05; AC-28442; AS-17054; HY-13330; rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide; SW219341-1; J-000994; J-524217; Q27074746; N-(5-(3,5-dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide, rel-; N-(5-(3,5-Dimethoxyphenethyl)-4H-pyrazol-3-yl)-4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzamide; N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]-Benzamide; N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]benzamide; N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin -1-yl]benzamide; N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide
    Click to Show/Hide
Indication
In total 2 Indication(s)
Gastric adenocarcinoma [ICD-11: 2B72]
Phase 2/3
[1]
HER2-positive breast cancer [ICD-11: 2C60-2C6Y]
Phase 2/3
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Lung cancer [ICD-11: 2C25]
[2]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[3]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
Endometrial cancer [ICD-11: 2C76]
[4]
Mature T-cell lymphoma [ICD-11: 2A90]
[5]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target Erbb2 tyrosine kinase receptor (HER2) ERBB2_HUMAN [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
8
IsoSMILES
C[C@@H]1CN(C[C@@H](N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC
InChI
InChI=1S/C26H33N5O3/c1-17-15-31(16-18(2)27-17)22-9-6-20(7-10-22)26(32)28-25-13-21(29-30-25)8-5-19-11-23(33-3)14-24(12-19)34-4/h6-7,9-14,17-18,27H,5,8,15-16H2,1-4H3,(H2,28,29,30,32)/t17-,18+
InChIKey
VRQMAABPASPXMW-HDICACEKSA-N
PubChem CID
51039095
ChEBI ID
CHEBI:63453
TTD Drug ID
D09GRX
DrugBank ID
DB12247
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  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) [1]
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
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M
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G
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440
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450
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M
T
L
L
A
A
G
N
V
V
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S
E
E
Y
L
E
E
L
L
460
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P
P
E
A
D
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K
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W
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E
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470
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D
A
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L
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T
L
L
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G
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K
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P
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L
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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
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T
V
V
A
A
V
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K
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M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
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D
K
K
D
D
L
L
520
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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
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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
|
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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L
L
590
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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
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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 Revealed Based on the Cell Line Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 Promega assay
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
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G
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S
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H
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450
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M
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M
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460
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P
P
E
A
D
D
P
P
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K
W
W
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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
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
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A
A
K
K
P
P
V
V
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T
V
V
A
A
V
V
K
K
M
M
510
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L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
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L
520
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S
D
D
L
L
V
V
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S
E
E
M
M
E
E
M
M
M
M
530
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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
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D
-
Y
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S
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F
-
580
|
D
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T
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C
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K
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P
-
P
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E
E
E
E
Q
Q
L
L
590
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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
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S
S
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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
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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
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L
L
G
G
G
G
S
S
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P
Y
Y
P
P
G
G
I
I
P
P
700
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V
V
E
E
E
E
L
L
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F
K
K
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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
|
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
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S
T
H
D
H
E
H
760
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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 AZD-4547 by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [6]
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
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M
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G
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S
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H
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H
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410
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Q
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P
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P
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A
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T
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420
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K
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R
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R
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Q
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430
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V
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S
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A
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E
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S
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S
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N
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440
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S
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T
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P
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V
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R
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I
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T
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450
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R
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S
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A
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460
|
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A
A
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G
V
V
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E
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Y
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E
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P
P
470
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E
E
D
D
P
P
K
K
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W
E
E
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F
P
P
R
R
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D
480
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K
K
L
L
T
T
L
L
G
G
K
K
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P
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L
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G
E
E
490
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G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
E
E
500
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A
A
V
V
G
G
I
I
D
D
K
K
D
D
K
K
P
P
K
K
510
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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
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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 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
Lung cancer [ICD-11: 2C25]
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 1 (FGFR1) [2]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V561M (c.1681G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.63  Å
PDB: 5EW8
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 5AM7
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.32
TM score: 0.98379
Amino acid change:
V561M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
G
V
A
A
G
G
460
|
V
V
S
S
E
E
Y
Y
E
E
L
L
P
P
E
E
D
D
P
P
470
|
R
R
W
W
E
E
L
L
P
P
R
R
D
D
R
R
L
L
V
V
480
|
L
L
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
490
|
G
G
Q
Q
V
V
V
V
L
L
A
A
E
E
A
A
I
I
G
G
500
|
L
L
D
D
K
K
D
D
K
K
P
P
N
N
R
R
V
V
T
T
510
|
K
K
V
V
A
A
V
V
K
K
M
M
L
L
K
K
S
S
D
D
520
|
A
A
T
T
E
E
K
K
D
D
L
L
S
S
D
D
L
L
I
I
530
|
S
S
E
E
M
M
E
E
M
M
M
M
K
K
M
M
I
I
G
G
540
|
K
K
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
550
|
A
A
C
C
T
T
Q
Q
D
D
G
G
P
P
L
L
Y
Y
V
V
560
|
I
I
V
M
E
E
Y
Y
A
A
S
S
K
K
G
G
N
N
L
L
570
|
R
R
E
E
Y
Y
L
L
Q
Q
A
A
R
R
R
R
P
P
P
P
580
|
G
G
L
L
E
E
Y
Y
S
S
Y
Y
N
N
P
P
S
S
H
H
590
|
N
N
P
P
E
E
E
E
Q
Q
L
L
S
S
S
S
K
K
D
D
600
|
L
L
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
610
|
G
G
M
M
E
E
Y
Y
L
L
A
A
S
S
K
K
K
K
C
C
620
|
I
I
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
630
|
L
L
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
640
|
A
A
D
D
F
F
G
G
L
L
A
A
R
R
D
D
I
I
H
H
650
|
H
H
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
T
T
N
N
660
|
G
G
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
670
|
E
E
A
A
L
L
F
F
D
D
R
R
I
I
Y
Y
T
T
H
H
680
|
Q
Q
S
S
D
D
V
V
W
W
S
S
F
F
G
G
V
V
L
L
690
|
L
L
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
700
|
P
P
Y
Y
P
P
G
G
V
V
P
P
V
V
E
E
E
E
L
L
710
|
F
F
K
K
L
L
L
L
K
K
E
E
G
G
H
H
R
R
M
M
720
|
D
D
K
K
P
P
S
S
N
N
C
C
T
T
N
N
E
E
L
L
730
|
Y
Y
M
M
M
M
M
M
R
R
D
D
C
C
W
W
H
H
A
A
740
|
V
V
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
750
|
L
L
V
V
E
E
D
D
L
L
D
D
R
R
I
I
V
V
A
A
760
|
L
L
T
T
S
S
N
N
Q
Q
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model L6 cells Skeletal muscle Rattus norvegicus (Rat) CVCL_0385
H1581 cells Lung Homo sapiens (Human) CVCL_1479
Experiment for
Molecule Alteration		 SDS-PAGE assay
Experiment for
Drug Resistance		 Transwell migration assay; Matrigel invasion assay; Proliferation assay; MTT assay
Mechanism Description The V561M mutation biases cells towards a more mesenchymal phenotype, including increased levels of proliferation, migration, invasion and anchorage-independent growth, which was confirmed using CyTOF, a novel single cell analysis tool. Using shRNA knockdown, loss of STAT3 restored sensitivity of cancer cells expressing V561M FGFR1 to AZD4547. Thus, the data demonstrate that combination therapies including FGFR and STAT3 may overcome V561M FGFR1 driven drug resistance in the clinic.
Endometrial cancer [ICD-11: 2C76]
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 2 (FGFR2) [4]
Resistant 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 Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MOLM-1 cells Bone marrow Homo sapiens (Human) CVCL_2188
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
In Vivo Model Female balb/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
Experiment for
Drug Resistance		 MTT assay; Soft-agar colony assay
References
Ref 1 Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical useOncotarget. 2016 Apr 26;7(17):24252-68. doi: 10.18632/oncotarget.8132.
Ref 2 The FGFR1 V561M Gatekeeper Mutation Drives AZD4547 Resistance through STAT3 Activation and EMTMol Cancer Res. 2019 Feb;17(2):532-543. doi: 10.1158/1541-7786.MCR-18-0429. Epub 2018 Sep 26.
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 Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial Cancer CellsMol Cancer Ther. 2015 Oct;14(10):2292-302. doi: 10.1158/1535-7163.MCT-15-0032. Epub 2015 Aug 20.
Ref 5 ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming. Acta Pharmacol Sin. 2023 Nov;44(11):2282-2295.
Ref 6 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.

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