Disease Information

General Information of the Disease (ID: DIS00377)
Name
Juvenile myelomonocytic leukaemia
ICD
ICD-11: 2A42
Type(s) of Resistant Mechanism of This Disease
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Cryptotanshinone
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: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]
Sensitive Disease Juvenile myelomonocytic leukaemia [ICD-11: 2A42.0]
Sensitive Drug Cryptotanshinone
 Drug Info 
Molecule Alteration Missense mutation
p.E76K (c.226G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5EHR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.62  Å
PDB: 6CRF
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.04
TM score: 0.6516
Amino acid change:
E76K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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0
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S
G
M
M
T
T
S
S
R
R
R
R
W
W
F
F
H
H
P
P
10
|
N
N
I
I
T
T
G
G
V
V
E
E
A
A
E
E
N
N
L
L
20
|
L
L
L
L
T
T
R
R
G
G
V
V
D
D
G
G
S
S
F
F
30
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L
L
A
A
R
R
P
P
S
S
K
K
S
S
N
N
P
P
G
G
40
|
D
D
F
F
T
T
L
L
S
S
V
V
R
R
R
R
N
N
G
G
50
|
A
A
V
V
T
T
H
H
I
I
K
K
I
I
Q
Q
N
N
T
T
60
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G
G
D
D
Y
Y
Y
Y
D
D
L
L
Y
Y
G
G
G
G
E
E
70
|
K
K
F
F
A
A
T
T
L
L
A
A
E
K
L
L
V
V
Q
Q
80
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Y
Y
Y
Y
M
M
E
E
H
H
H
H
G
G
Q
Q
L
L
K
K
90
|
E
E
K
K
N
N
G
G
D
D
V
V
I
I
E
E
L
L
K
K
100
|
Y
Y
P
P
L
L
N
N
C
C
A
A
D
D
P
P
T
T
S
S
110
|
E
E
R
R
W
W
F
F
H
H
G
G
H
H
L
L
S
S
G
G
120
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K
K
E
E
A
A
E
E
K
K
L
L
L
L
T
T
E
E
K
K
130
|
G
G
K
K
H
H
G
G
S
S
F
F
L
L
V
V
R
R
E
E
140
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S
S
Q
Q
S
S
H
H
P
P
G
G
D
D
F
F
V
V
L
L
150
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S
S
V
V
R
R
T
T
G
G
D
D
D
D
K
K
G
G
E
E
160
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S
S
N
N
D
D
G
G
K
K
S
S
K
K
V
V
T
T
H
H
170
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V
V
M
M
I
I
R
R
C
C
Q
Q
E
E
L
L
K
K
Y
Y
180
|
D
D
V
V
G
G
G
G
G
G
E
E
R
R
F
F
D
D
S
S
190
|
L
L
T
T
D
D
L
L
V
V
E
E
H
H
Y
Y
K
K
K
K
200
|
N
N
P
P
M
M
V
V
E
E
T
T
L
L
G
G
T
T
V
V
210
|
L
L
Q
Q
L
L
K
K
Q
Q
P
P
L
L
N
N
T
T
T
T
220
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R
R
I
I
N
N
A
A
A
A
E
E
I
I
E
E
S
S
R
R
230
|
V
V
R
R
E
E
L
L
S
S
K
K
L
L
A
A
E
E
T
T
240
|
T
T
D
D
K
K
V
V
K
K
Q
Q
G
G
F
F
W
W
E
E
250
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E
E
F
F
E
E
T
T
L
L
Q
Q
Q
Q
Q
Q
E
E
C
C
260
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K
K
L
L
L
L
Y
Y
S
S
R
R
K
K
E
E
G
G
Q
Q
270
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R
R
Q
Q
E
E
N
N
K
K
N
N
K
K
N
N
R
R
Y
Y
280
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K
K
N
N
I
I
L
L
P
P
F
F
D
D
H
H
T
T
R
R
290
|
V
V
V
V
L
L
H
H
D
D
G
G
D
D
P
P
N
N
E
E
300
|
P
P
V
V
S
S
D
D
Y
Y
I
I
N
N
A
A
N
N
I
I
310
|
I
I
M
M
P
P
E
E
F
F
E
E
T
T
K
K
C
C
N
N
320
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N
N
S
S
K
K
P
P
K
K
K
K
S
S
Y
Y
I
I
A
A
330
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T
T
Q
Q
G
G
C
C
L
L
Q
Q
N
N
T
T
V
V
N
N
340
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D
D
F
F
W
W
R
R
M
M
V
V
F
F
Q
Q
E
E
N
N
350
|
S
S
R
R
V
V
I
I
V
V
M
M
T
T
T
T
K
K
E
E
360
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V
V
E
E
R
R
G
G
K
K
S
S
K
K
C
C
V
V
K
K
370
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Y
Y
W
W
P
P
D
D
E
E
Y
Y
A
A
L
L
K
K
E
E
380
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Y
Y
G
G
V
V
M
M
R
R
V
V
R
R
N
N
V
V
K
K
390
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E
E
S
S
A
A
A
A
H
H
D
D
Y
Y
T
T
L
L
R
R
400
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E
E
L
L
K
K
L
L
S
S
K
K
V
V
G
G
Q
Q
G
G
410
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N
N
T
T
E
E
R
R
T
T
V
V
W
W
Q
Q
Y
Y
H
H
420
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F
F
R
R
T
T
W
W
P
P
D
D
H
H
G
G
V
V
P
P
430
|
S
S
D
D
P
P
G
G
G
G
V
V
L
L
D
D
F
F
L
L
440
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E
E
E
E
V
V
H
H
H
H
K
K
Q
Q
E
E
S
S
I
I
450
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M
M
D
D
A
A
G
G
P
P
V
V
V
V
V
V
H
H
C
C
460
|
S
S
A
A
G
G
I
I
G
G
R
R
T
T
G
G
T
T
F
F
470
|
I
I
V
V
I
I
D
D
I
I
L
L
I
I
D
D
I
I
I
I
480
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R
R
E
E
K
K
G
G
V
V
D
D
C
C
D
D
I
I
D
D
490
|
V
V
P
P
K
K
T
T
I
I
Q
Q
M
M
V
V
R
R
S
S
500
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Q
Q
R
R
S
S
G
G
M
M
V
V
Q
Q
T
T
E
E
A
A
510
|
Q
Q
Y
Y
R
R
F
F
I
I
Y
Y
M
M
A
A
V
V
Q
Q
520
|
H
H
Y
Y
I
I
E
E
T
T
L
L
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter 96 aqueous one solution cell proliferation assay
Mechanism Description The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of Cryptotanshinone by unusual activation of pro-survival pathway
References
Ref 1 Identification of cryptotanshinone as an inhibitor of oncogenic protein tyrosine phosphatase SHP2 (PTPN11)J Med Chem. 2013 Sep 26;56(18):7212-21. doi: 10.1021/jm400474r. Epub 2013 Sep 4.

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