Disease Information

General Information of the Disease (ID: DIS00099)
Name
Bladder cancer
ICD
ICD-11: 2C94
Resistance Map
Type(s) of Resistant Mechanism of This Disease with Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
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: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [1]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
Resistant Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.09  Å
PDB: 3WLW
Mutant Type Structure Method: Electron microscopy Resolution: 3.09  Å
PDB: 7MN6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.33
TM score: 0.96205
Amino acid change:
S310F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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90
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120
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130
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140
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160
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170
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190
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220
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230
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240
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260
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280
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290
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310
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320
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480
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570
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590
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720
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750
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760
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770
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780
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790
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800
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820
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830
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840
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850
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860
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870
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880
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890
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900
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910
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920
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940
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950
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960
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970
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980
|
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990
|
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1000
|
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-
Y
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1010
|
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1020
|
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1030
|
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-
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1040
|
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1050
|
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-
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1060
|
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N
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-
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1070
|
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1080
|
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1090
|
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1100
|
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1110
|
-
W
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-
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-
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-
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1120
|
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1130
|
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1140
|
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1150
|
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1160
|
-
A
-
L
-
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-
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-
N
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1170
|
-
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-
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E
-
E
1180
|
-
I
-
P
-
A
-
L
-
D
-
K
-
E
-
L
-
K
-
A
1190
|
-
K
-
G
-
K
-
S
-
A
-
L
-
M
-
F
-
N
-
L
1200
|
-
Q
-
E
-
P
-
Y
-
F
-
T
-
W
-
P
-
L
-
I
1210
|
-
A
-
A
-
D
-
G
-
G
-
Y
-
A
-
F
-
K
-
Y
1220
|
-
E
-
N
-
G
-
K
-
Y
-
D
-
I
-
K
-
D
-
V
1230
|
-
G
-
V
-
D
-
N
-
A
-
G
-
A
-
K
-
A
-
G
1240
|
-
L
-
T
-
F
-
L
-
V
-
D
-
L
-
I
-
K
-
N
1250
|
-
K
-
H
-
M
-
N
-
A
-
D
-
T
-
D
-
Y
-
S
1260
|
-
I
-
A
-
E
-
A
-
A
-
F
-
N
-
K
-
G
-
E
1270
|
-
T
-
A
-
M
-
T
-
I
-
N
-
G
-
P
-
W
-
A
1280
|
-
W
-
S
-
N
-
I
-
D
-
T
-
S
-
K
-
V
-
N
1290
|
-
Y
-
G
-
V
-
T
-
V
-
L
-
P
-
T
-
F
-
K
1300
|
-
G
-
Q
-
P
-
S
-
K
-
P
-
F
-
V
-
G
-
V
1310
|
-
L
-
S
-
A
-
G
-
I
-
N
-
A
-
A
-
S
-
P
1320
|
-
N
-
K
-
E
-
L
-
A
-
K
-
E
-
F
-
L
-
E
1330
|
-
N
-
Y
-
L
-
L
-
T
-
D
-
E
-
G
-
L
-
E
1340
|
-
A
-
V
-
N
-
K
-
D
-
K
-
P
-
L
-
G
-
A
1350
|
-
V
-
A
-
L
-
K
-
S
-
Y
-
E
-
E
-
E
-
L
1360
|
-
A
-
K
-
D
-
P
-
R
-
I
-
A
-
A
-
T
-
M
1370
|
-
E
-
N
-
A
-
Q
-
K
-
G
-
E
-
I
-
M
-
P
1380
|
-
N
-
I
-
P
-
Q
-
M
-
S
-
A
-
F
-
W
-
Y
1390
|
-
A
-
V
-
R
-
T
-
A
-
V
-
I
-
N
-
A
-
A
1400
|
-
S
-
G
-
R
-
Q
-
T
-
V
-
D
-
E
-
A
-
L
1410
|
-
K
-
D
-
A
-
Q
-
T
-
N
-
S
-
S
-
S
-
S
1420
|
-
G
-
P
-
S
-
S
-
P
-
S
-
A
-
W
-
S
-
H
1430
|
-
P
-
Q
-
F
-
E
-
K
-
G
-
G
-
G
-
S
-
G
1440
|
-
G
-
G
-
S
-
G
-
G
-
S
-
S
-
A
-
W
-
S
1450
|
-
H
-
P
-
Q
-
F
-
E
-
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Preclinical Drug(s)
3 drug(s) in total
Click to Show/Hide the Full List of Drugs
Binimetinib/Everolimus
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: GTPase Hras (HRAS) [2]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Binimetinib/Everolimus
 Drug Info 
Molecule Alteration Missense mutation
p.G12V (c.35G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 7SCW
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7SCX
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99104
Amino acid change:
G12V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
V
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
S
S
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
170
|
M
M
S
S
K
K
D
D
G
G
K
K
K
K
K
K
K
K
K
K
180
|
K
K
S
S
K
K
T
T
K
K
C
C
V
V
I
I
M
M
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model T24 cells Bladder Homo sapiens (Human) CVCL_0554
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
RL952 cells Endometrium Homo sapiens (Human) CVCL_0505
NCI-H1915 cells Lung Homo sapiens (Human) CVCL_1505
KYSE-30 cells Esophagus Homo sapiens (Human) CVCL_1351
KNS62 cells Brain Homo sapiens (Human) CVCL_1335
HCC78 cells Pleural effusion Homo sapiens (Human) CVCL_2061
HCC44 cells Lung Homo sapiens (Human) CVCL_2060
CAL-12T cells Lung Homo sapiens (Human) CVCL_1105
In Vivo Model CB17 SCID-/- mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay
Cisplatin/Pictilisib
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: PI3-kinase alpha (PIK3CA) [3]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Cisplatin/Pictilisib
 Drug Info 
Molecule Alteration Missense mutation
p.H1047R (c.3140A>G)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 2.41  Å
PDB: 8DCP
Mutant Type Structure Method: X-ray diffraction Resolution: 2.61  Å
PDB: 8V8V
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.09
TM score: 0.95656
Amino acid change:
H1047R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
S
-
Y
-
Y
-
H
-
H
-
H
-
-20
|
H
-
H
-
H
-
D
-
Y
-
D
-
I
-
P
-
T
-
T
-
-10
|
E
-
N
-
L
-
Y
-
F
-
Q
-
G
G
A
A
M
M
G
G
0
|
S
S
M
M
P
P
P
P
R
R
P
P
S
S
S
S
G
G
E
E
10
|
L
L
W
W
G
G
I
I
H
H
L
L
M
M
P
P
P
P
R
R
20
|
I
I
L
L
V
V
E
E
C
C
L
L
L
L
P
P
N
N
G
G
30
|
M
M
I
I
V
V
T
T
L
L
E
E
C
C
L
L
R
R
E
E
40
|
A
A
T
T
L
L
I
I
T
T
I
I
K
K
H
H
E
E
L
L
50
|
F
F
K
K
E
E
A
A
R
R
K
K
Y
Y
P
P
L
L
H
H
60
|
Q
Q
L
L
L
L
Q
Q
D
D
E
E
S
S
S
S
Y
Y
I
I
70
|
F
F
V
V
S
S
V
V
T
T
Q
Q
E
E
A
A
E
E
R
R
80
|
E
E
E
E
F
F
F
F
D
D
E
E
T
T
R
R
R
R
L
L
90
|
C
C
D
D
L
L
R
R
L
L
F
F
Q
Q
P
P
F
F
L
L
100
|
K
K
V
V
I
I
E
E
P
P
V
V
G
G
N
N
R
R
E
E
110
|
E
E
K
K
I
I
L
L
N
N
R
R
E
E
I
I
G
G
F
F
120
|
A
A
I
I
G
G
M
M
P
P
V
V
C
C
E
E
F
F
D
D
130
|
M
M
V
V
K
K
D
D
P
P
E
E
V
V
Q
Q
D
D
F
F
140
|
R
R
R
R
N
N
I
I
L
L
N
N
V
V
C
C
K
K
E
E
150
|
A
A
V
V
D
D
L
L
R
R
D
D
L
L
N
N
S
S
P
P
160
|
H
H
S
S
R
R
A
A
M
M
Y
Y
V
V
Y
Y
P
P
P
P
170
|
N
N
V
V
E
E
S
S
S
S
P
P
E
E
L
L
P
P
K
K
180
|
H
H
I
I
Y
Y
N
N
K
K
L
L
D
D
K
K
G
G
Q
Q
190
|
I
I
I
I
V
V
V
V
I
I
W
W
V
V
I
I
V
V
S
S
200
|
P
P
N
N
N
N
D
D
K
K
Q
Q
K
K
Y
Y
T
T
L
L
210
|
K
K
I
I
N
N
H
H
D
D
C
C
V
V
P
P
E
E
Q
Q
220
|
V
V
I
I
A
A
E
E
A
A
I
I
R
R
K
K
K
K
T
T
230
|
R
R
S
S
M
M
L
L
L
L
S
S
S
S
E
E
Q
Q
L
L
240
|
K
K
L
L
C
C
V
V
L
L
E
E
Y
Y
Q
Q
G
G
K
K
250
|
Y
Y
I
I
L
L
K
K
V
V
C
C
G
G
C
C
D
D
E
E
260
|
Y
Y
F
F
L
L
E
E
K
K
Y
Y
P
P
L
L
S
S
Q
Q
270
|
Y
Y
K
K
Y
Y
I
I
R
R
S
S
C
C
I
I
M
M
L
L
280
|
G
G
R
R
M
M
P
P
N
N
L
L
M
M
L
L
M
M
A
A
290
|
K
K
E
E
S
S
L
L
Y
Y
S
S
Q
Q
L
L
P
P
M
M
300
|
D
D
C
C
F
F
T
T
M
M
P
P
S
S
Y
Y
S
S
R
R
310
|
R
R
I
I
S
S
T
T
A
A
T
T
P
P
Y
Y
M
M
N
N
320
|
G
G
E
E
T
T
S
S
T
T
K
K
S
S
L
L
W
W
V
V
330
|
I
I
N
N
S
S
A
A
L
L
R
R
I
I
K
K
I
I
L
L
340
|
C
C
A
A
T
T
Y
Y
V
V
N
N
V
V
N
N
I
I
R
R
350
|
D
D
I
I
D
D
K
K
I
I
Y
Y
V
V
R
R
T
T
G
G
360
|
I
I
Y
Y
H
H
G
G
G
G
E
E
P
P
L
L
C
C
D
D
370
|
N
N
V
V
N
N
T
T
Q
Q
R
R
V
V
P
P
C
C
S
S
380
|
N
N
P
P
R
R
W
W
N
N
E
E
W
W
L
L
N
N
Y
Y
390
|
D
D
I
I
Y
Y
I
I
P
P
D
D
L
L
P
P
R
R
A
A
400
|
A
A
R
R
L
L
C
C
L
L
S
S
I
I
C
C
S
S
V
V
410
|
K
K
G
G
R
R
K
K
G
G
A
A
K
K
E
E
E
E
H
H
420
|
C
C
P
P
L
L
A
A
W
W
G
G
N
N
I
I
N
N
L
L
430
|
F
F
D
D
Y
Y
T
T
D
D
T
T
L
L
V
V
S
S
G
G
440
|
K
K
M
M
A
A
L
L
N
N
L
L
W
W
P
P
V
V
P
P
450
|
H
H
G
G
L
L
E
E
D
D
L
L
L
L
N
N
P
P
I
I
460
|
G
G
V
V
T
T
G
G
S
S
N
N
P
P
N
N
K
K
E
E
470
|
T
T
P
P
C
C
L
L
E
E
L
L
E
E
F
F
D
D
W
W
480
|
F
F
S
S
S
S
V
V
V
V
K
K
F
F
P
P
D
D
M
M
490
|
S
S
V
V
I
I
E
E
E
E
H
H
A
A
N
N
W
W
S
S
500
|
V
V
S
S
R
R
E
E
A
A
G
G
F
F
S
S
Y
Y
S
S
510
|
H
H
A
A
G
G
L
L
S
S
N
N
R
R
L
L
A
A
R
R
520
|
D
D
N
N
E
E
L
L
R
R
E
E
N
N
D
D
K
K
E
E
530
|
Q
Q
L
L
K
K
A
A
I
I
S
S
T
T
R
R
D
D
P
P
540
|
L
L
S
S
E
E
I
I
T
T
E
E
Q
Q
E
E
K
K
D
D
550
|
F
F
L
L
W
W
S
S
H
H
R
R
H
H
Y
Y
C
C
V
V
560
|
T
T
I
I
P
P
E
E
I
I
L
L
P
P
K
K
L
L
L
L
570
|
L
L
S
S
V
V
K
K
W
W
N
N
S
S
R
R
D
D
E
E
580
|
V
V
A
A
Q
Q
M
M
Y
Y
C
C
L
L
V
V
K
K
D
D
590
|
W
W
P
P
P
P
I
I
K
K
P
P
E
E
Q
Q
A
A
M
M
600
|
E
E
L
L
L
L
D
D
C
C
N
N
Y
Y
P
P
D
D
P
P
610
|
M
M
V
V
R
R
G
G
F
F
A
A
V
V
R
R
C
C
L
L
620
|
E
E
K
K
Y
Y
L
L
T
T
D
D
D
D
K
K
L
L
S
S
630
|
Q
Q
Y
Y
L
L
I
I
Q
Q
L
L
V
V
Q
Q
V
V
L
L
640
|
K
K
Y
Y
E
E
Q
Q
Y
Y
L
L
D
D
N
N
L
L
L
L
650
|
V
V
R
R
F
F
L
L
L
L
K
K
K
K
A
A
L
L
T
T
660
|
N
N
Q
Q
R
R
I
I
G
G
H
H
F
F
F
F
F
F
W
W
670
|
H
H
L
L
K
K
S
S
E
E
M
M
H
H
N
N
K
K
T
T
680
|
V
V
S
S
Q
Q
R
R
F
F
G
G
L
L
L
L
L
L
E
E
690
|
S
S
Y
Y
C
C
R
R
A
A
C
C
G
G
M
M
Y
Y
L
L
700
|
K
K
H
H
L
L
N
N
R
R
Q
Q
V
V
E
E
A
A
M
M
710
|
E
E
K
K
L
L
I
I
N
N
L
L
T
T
D
D
I
I
L
L
720
|
K
K
Q
Q
E
E
K
K
K
K
D
D
E
E
T
T
Q
Q
K
K
730
|
V
V
Q
Q
M
M
K
K
F
F
L
L
V
V
E
E
Q
Q
M
M
740
|
R
R
R
R
P
P
D
D
F
F
M
M
D
D
A
A
L
L
Q
Q
750
|
G
G
F
F
L
L
S
S
P
P
L
L
N
N
P
P
A
A
H
H
760
|
Q
Q
L
L
G
G
N
N
L
L
R
R
L
L
E
E
E
E
C
C
770
|
R
R
I
I
M
M
S
S
S
S
A
A
K
K
R
R
P
P
L
L
780
|
W
W
L
L
N
N
W
W
E
E
N
N
P
P
D
D
I
I
M
M
790
|
S
S
E
E
L
L
L
L
F
F
Q
Q
N
N
N
N
E
E
I
I
800
|
I
I
F
F
K
K
N
N
G
G
D
D
D
D
L
L
R
R
Q
Q
810
|
D
D
M
M
L
L
T
T
L
L
Q
Q
I
I
I
I
R
R
I
I
820
|
M
M
E
E
N
N
I
I
W
W
Q
Q
N
N
Q
Q
G
G
L
L
830
|
D
D
L
L
R
R
M
M
L
L
P
P
Y
Y
G
G
C
C
L
L
840
|
S
S
I
I
G
G
D
D
C
C
V
V
G
G
L
L
I
I
E
E
850
|
V
V
V
V
R
R
N
N
S
S
H
H
T
T
I
I
M
M
Q
Q
860
|
I
I
Q
Q
C
C
K
K
G
G
G
G
L
L
K
K
G
G
A
A
870
|
L
L
Q
Q
F
F
N
N
S
S
H
H
T
T
L
L
H
H
Q
Q
880
|
W
W
L
L
K
K
D
D
K
K
N
N
K
K
G
G
E
E
I
I
890
|
Y
Y
D
D
A
A
A
A
I
I
D
D
L
L
F
F
T
T
R
R
900
|
S
S
C
C
A
A
G
G
Y
Y
C
C
V
V
A
A
T
T
F
F
910
|
I
I
L
L
G
G
I
I
G
G
D
D
R
R
H
H
N
N
S
S
920
|
N
N
I
I
M
M
V
V
K
K
D
D
D
D
G
G
Q
Q
L
L
930
|
F
F
H
H
I
I
D
D
F
F
G
G
H
H
F
F
L
L
D
D
940
|
H
H
K
K
K
K
K
K
K
K
F
F
G
G
Y
Y
K
K
R
R
950
|
E
E
R
R
V
V
P
P
F
F
V
V
L
L
T
T
Q
Q
D
D
960
|
F
F
L
L
I
I
V
V
I
I
S
S
K
K
G
G
A
A
Q
Q
970
|
E
E
C
C
T
T
K
K
T
T
R
R
E
E
F
F
E
E
R
R
980
|
F
F
Q
Q
E
E
M
M
C
C
Y
Y
K
K
A
A
Y
Y
L
L
990
|
A
A
I
I
R
R
Q
Q
H
H
A
A
N
N
L
L
F
F
I
I
1000
|
N
N
L
L
F
F
S
S
M
M
M
M
L
L
G
G
S
S
G
G
1010
|
M
M
P
P
E
E
L
L
Q
Q
S
S
F
F
D
D
D
D
I
I
1020
|
A
A
Y
Y
I
I
R
R
K
K
T
T
L
L
A
A
L
L
D
D
1030
|
K
K
T
T
E
E
Q
Q
E
E
A
A
L
L
E
E
Y
Y
F
F
1040
|
M
M
K
K
Q
Q
M
M
N
N
D
D
A
A
H
R
H
H
G
G
1050
|
G
G
W
W
T
T
T
T
K
K
M
M
D
D
W
W
I
I
F
F
1060
|
H
H
T
T
I
I
K
K
Q
Q
H
H
A
A
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MEK/ERK signaling pathway Inhibition hsa04011
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
In Vivo Model NSG mouse PDX model Mus musculus
Experiment for
Drug Resistance		 MTS assay; FACS assay
Mechanism Description Pictilisib activated the compensatory MEK/ERK pathways that likely contributed to pictilisib resistance, which was reversed by co-treatment with the RAF inhibitor sorafenib. RNA-sequencing of tumors resistant to treatment suggested that LSP1 down-regulation correlated with drug resistance.
Everolimus/Selumetinib
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: GTPase Hras (HRAS) [2]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Everolimus/Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.G12V (c.35G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 7SCW
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7SCX
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99104
Amino acid change:
G12V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
V
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
S
S
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
170
|
M
M
S
S
K
K
D
D
G
G
K
K
K
K
K
K
K
K
K
K
180
|
K
K
S
S
K
K
T
T
K
K
C
C
V
V
I
I
M
M
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model T24 cells Bladder Homo sapiens (Human) CVCL_0554
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
RL952 cells Endometrium Homo sapiens (Human) CVCL_0505
NCI-H1915 cells Lung Homo sapiens (Human) CVCL_1505
KYSE-30 cells Esophagus Homo sapiens (Human) CVCL_1351
KNS62 cells Brain Homo sapiens (Human) CVCL_1335
HCC78 cells Pleural effusion Homo sapiens (Human) CVCL_2061
HCC44 cells Lung Homo sapiens (Human) CVCL_2060
CAL-12T cells Lung Homo sapiens (Human) CVCL_1105
In Vivo Model CB17 SCID-/- mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay
References
Ref 1 Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinibCancer Biol Ther. 2014 Sep;15(9):1239-47. doi: 10.4161/cbt.29687. Epub 2014 Jul 14.
Ref 2 Mutant HRAS as novel target for MEK and mTOR inhibitorsOncotarget. 2015 Dec 8;6(39):42183-96. doi: 10.18632/oncotarget.5619.
Ref 3 The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder CancerClin Cancer Res. 2017 Nov 1;23(21):6580-6591. doi: 10.1158/1078-0432.CCR-17-0033. Epub 2017 Aug 14.

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