Disease Information

General Information of the Disease (ID: DIS00367)
Name
Hematologic cancer
ICD
ICD-11: 2B3Z
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)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Enasidenib
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: Isocitrate dehydrogenase NADP 2 (IDH2) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Sensitive Drug Enasidenib
 Drug Info 
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIS
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.29352
Amino acid change:
R172K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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40
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A
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60
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70
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80
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90
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D
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100
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110
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120
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130
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140
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150
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I
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C
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K
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N
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I
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P
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R
160
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L
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P
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G
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W
T
T
K
K
P
P
I
I
T
T
170
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I
I
G
G
S
K
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
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K
K
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A
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T
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A
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190
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200
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E
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210
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Y
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N
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F
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P
-
A
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G
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G
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V
-
G
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M
220
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G
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M
-
Y
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N
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T
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D
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E
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I
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S
230
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G
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A
240
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K
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L
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250
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T
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I
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A
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D
260
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G
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I
270
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F
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D
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K
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H
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Y
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D
280
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K
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N
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K
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I
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W
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Y
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E
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L
290
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I
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300
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S
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G
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310
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N
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Y
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320
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330
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340
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350
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360
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370
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380
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390
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400
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410
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420
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H
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430
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440
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T
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450
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460
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H
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H
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H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
II-B08
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) [2]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Sensitive Drug II-B08
 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
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R
R
R
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H
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P
10
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N
N
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G
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E
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L
L
20
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L
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G
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G
G
50
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K
I
I
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Q
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N
T
T
60
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G
G
D
D
Y
Y
Y
Y
D
D
L
L
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Y
G
G
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G
E
E
70
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K
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A
A
T
T
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90
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D
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K
100
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Y
Y
P
P
L
L
N
N
C
C
A
A
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D
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P
T
T
S
S
110
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E
E
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R
W
W
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F
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G
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G
G
120
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K
K
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E
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L
L
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T
E
E
K
K
130
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G
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E
140
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150
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R
T
T
G
G
D
D
D
D
K
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G
G
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E
160
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S
N
N
D
D
G
G
K
K
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S
K
K
V
V
T
T
H
H
170
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V
V
M
M
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I
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C
Q
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E
E
L
L
K
K
Y
Y
180
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D
D
V
V
G
G
G
G
G
G
E
E
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R
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F
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D
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S
190
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L
L
T
T
D
D
L
L
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E
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H
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Y
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K
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200
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N
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P
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M
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V
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E
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T
L
L
G
G
T
T
V
V
210
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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
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V
V
R
R
E
E
L
L
S
S
K
K
L
L
A
A
E
E
T
T
240
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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
|
R
R
Q
Q
E
E
N
N
K
K
N
N
K
K
N
N
R
R
Y
Y
280
|
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
|
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
|
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
|
E
E
L
L
K
K
L
L
S
S
K
K
V
V
G
G
Q
Q
G
G
410
|
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
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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
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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
|
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 HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 3H-thymidine incorporation assay
Mechanism Description The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of II-B08 by unusual activation of pro-survival pathway
References
Ref 1 Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: Preliminary results from KEYNOTE-0280.
Ref 2 Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)J Med Chem. 2010 Mar 25;53(6):2482-93. doi: 10.1021/jm901645u.

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