Disease Information

General Information of the Disease (ID: DIS00093)
Name
Endometrial cancer
ICD
ICD-11: 2C76
Resistance Map
Type(s) of Resistant Mechanism of This Disease with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Clinical Trial Drug(s)
9 drug(s) in total
Click to Show/Hide the Full List of Drugs
Brivanib
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 2 (FGFR2) [1]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Brivanib
 Drug 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 SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Brivanib by unusual activation of pro-survival pathway
Capivasertib
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: RAC-alpha serine/threonine-protein kinase (AKT1) [2]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Capivasertib
 Drug Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Capivasertib by aberration of the drug's therapeutic target
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [3]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Capivasertib
 Drug Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Breast N.A.
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Capivasertib by aberration of the drug's therapeutic target
Cediranib
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 2 (FGFR2) [1]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Cediranib
 Drug 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 SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Derazantinib
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 2 (FGFR2) [4]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Derazantinib
 Drug 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
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model A2780 cells Ovary Homo sapiens (Human) CVCL_0134
KG-1 cells Bone marrow Homo sapiens (Human) CVCL_0374
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
AN3CA cells Ovary Homo sapiens (Human) CVCL_0028
SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
K562 cells Blood Homo sapiens (Human) CVCL_0004
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
RT-112 cells Urinary bladder Homo sapiens (Human) CVCL_1670
MFM-223 cells Pleural effusion Homo sapiens (Human) CVCL_1408
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
COS-1 cells Kidney Chlorocebus aethiops (Green monkey) CVCL_0223
In Vivo Model SCID beige mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.
Selumetinib
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) [5]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Resistant Drug Selumetinib
 Drug 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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
AZD-4547
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) [6]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Resistant Drug AZD-4547
 Drug 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
DEBIO-1347
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) [7]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug DEBIO-1347
 Drug 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
Miransertib
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: RAC-alpha serine/threonine-protein kinase (AKT1) [8]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug Miransertib
 Drug Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
RO-5126766 free base
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 2 (FGFR2) [5]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug RO-5126766 free base
 Drug 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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Preclinical Drug(s)
3 drug(s) in total
Click to Show/Hide the Full List of Drugs
ARQ 751
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: RAC-alpha serine/threonine-protein kinase (AKT1) [8]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug ARQ 751
 Drug Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target
E7090
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) [9]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug E7090
 Drug 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
GSK3052230
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) [10]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Sensitive Drug GSK3052230
 Drug 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 Lung N.A.
Experiment for
Molecule Alteration		 QuantiGene Plex DNA assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of GSK3052230 by aberration of the drug's therapeutic target
References
Ref 1 Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
Ref 2 Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic backgroundMol Cancer Ther. 2012 Apr;11(4):873-87. doi: 10.1158/1535-7163.MCT-11-0824-T. Epub 2012 Jan 31.
Ref 3 Capivasertib Active against AKT1-Mutated CancersCancer Discov. 2019 Jan;9(1):OF7. doi: 10.1158/2159-8290.CD-NB2018-153. Epub 2018 Nov 14.
Ref 4 Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR DysregulationPLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. eCollection 2016.
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