Disease Information

General Information of the Disease (ID: DIS00052)
Name
Acute myeloid leukemia
ICD
ICD-11: 2A60
Resistance Map
Type(s) of Resistant Mechanism of This Disease with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  DISM: Drug Inactivation by Structure Modification
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
5 drug(s) in total
Click to Show/Hide the Full List of Drugs
Daunorubicin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA (cytosine-5)-methyltransferase 3A (DNMT3A) [1]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Resistant Drug Daunorubicin
 Drug Info 
Molecule Alteration Missense mutation
p.R882H
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 6W8B
Mutant Type Structure Method: X-ray diffraction Resolution: 2.44  Å
PDB: 6W8J
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.46
TM score: 0.99493
Amino acid change:
R882H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
A
A
E
E
630
|
K
K
R
R
K
K
P
P
I
I
R
R
V
V
L
L
S
S
L
L
640
|
F
F
D
D
G
G
I
I
A
A
T
T
G
G
L
L
L
L
V
V
650
|
L
L
K
K
D
D
L
L
G
G
I
I
Q
Q
V
V
D
D
R
R
660
|
Y
Y
I
I
A
A
S
S
E
E
V
V
C
C
E
E
D
D
S
S
670
|
I
I
T
T
V
V
G
G
M
M
V
V
R
R
H
H
Q
Q
G
G
680
|
K
K
I
I
M
M
Y
Y
V
V
G
G
D
D
V
V
R
R
S
S
690
|
V
V
T
T
Q
Q
K
K
H
H
I
I
Q
Q
E
E
W
W
G
G
700
|
P
P
F
F
D
D
L
L
V
V
I
I
G
G
G
G
S
S
P
P
710
|
C
C
N
N
D
D
L
L
S
S
I
I
V
V
N
N
P
P
A
A
720
|
R
R
K
K
G
G
L
L
Y
Y
E
E
G
G
T
T
G
G
R
R
730
|
L
L
F
F
F
F
E
E
F
F
Y
Y
R
R
L
L
L
L
H
H
740
|
D
D
A
A
R
R
P
P
K
K
E
E
G
G
D
D
D
D
R
R
750
|
P
P
F
F
F
F
W
W
L
L
F
F
E
E
N
N
V
V
V
V
760
|
A
A
M
M
G
G
V
V
S
S
D
D
K
K
R
R
D
D
I
I
770
|
S
S
R
R
F
F
L
L
E
E
S
S
N
N
P
P
V
V
M
M
780
|
I
I
D
D
A
A
K
K
E
E
V
V
S
S
A
A
A
A
H
H
790
|
R
R
A
A
R
R
Y
Y
F
F
W
W
G
G
N
N
L
L
P
P
800
|
G
G
M
M
N
N
R
R
P
P
L
L
A
A
S
S
T
T
V
V
810
|
N
N
D
D
K
K
L
L
E
E
L
L
Q
Q
E
E
C
C
L
L
820
|
E
E
H
H
G
G
R
R
I
I
A
A
K
K
F
F
S
S
K
K
830
|
V
V
R
R
T
T
I
I
T
T
T
T
R
R
S
S
N
N
S
S
840
|
I
I
K
K
Q
Q
G
G
K
K
D
D
Q
Q
H
H
F
F
P
P
850
|
V
V
F
F
M
M
N
N
E
E
K
K
E
E
D
D
I
I
L
L
860
|
W
W
C
C
T
T
E
E
M
M
E
E
R
R
V
V
F
F
G
G
870
|
F
F
P
P
V
V
H
H
Y
Y
T
T
D
D
V
V
S
S
N
N
880
|
M
M
S
S
R
H
L
L
A
A
R
R
Q
Q
R
R
L
L
L
L
890
|
G
G
R
R
S
S
W
W
S
S
V
V
P
P
V
V
I
I
R
R
900
|
H
H
L
L
F
F
A
A
P
P
L
L
K
K
E
E
Y
Y
F
F
910
|
A
A
C
C
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ADAM9/EGFR signaling pathway Inhibition hsa01521
AKT signaling pathway Inhibition hsa04151
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Mechanism Description DNMT3A mutations are most common in AML. DNMT3A mutant AML has been linked to anthracycline resistance and poor prognosis in some studies. Many of these mutations occur in genes with established roles in the regulation and maintenance of DNA methylation and/or chromatin modifications in hematopoietic stem/progenitor cells.
Idarubicin
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: DNA (cytosine-5)-methyltransferase 3A (DNMT3A) [2]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug Idarubicin
 Drug Info 
Molecule Alteration Missense mutation
p.R882H (c.2645G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 6W8B
Mutant Type Structure Method: X-ray diffraction Resolution: 2.44  Å
PDB: 6W8J
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.46
TM score: 0.99493
Amino acid change:
R882H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
A
A
E
E
630
|
K
K
R
R
K
K
P
P
I
I
R
R
V
V
L
L
S
S
L
L
640
|
F
F
D
D
G
G
I
I
A
A
T
T
G
G
L
L
L
L
V
V
650
|
L
L
K
K
D
D
L
L
G
G
I
I
Q
Q
V
V
D
D
R
R
660
|
Y
Y
I
I
A
A
S
S
E
E
V
V
C
C
E
E
D
D
S
S
670
|
I
I
T
T
V
V
G
G
M
M
V
V
R
R
H
H
Q
Q
G
G
680
|
K
K
I
I
M
M
Y
Y
V
V
G
G
D
D
V
V
R
R
S
S
690
|
V
V
T
T
Q
Q
K
K
H
H
I
I
Q
Q
E
E
W
W
G
G
700
|
P
P
F
F
D
D
L
L
V
V
I
I
G
G
G
G
S
S
P
P
710
|
C
C
N
N
D
D
L
L
S
S
I
I
V
V
N
N
P
P
A
A
720
|
R
R
K
K
G
G
L
L
Y
Y
E
E
G
G
T
T
G
G
R
R
730
|
L
L
F
F
F
F
E
E
F
F
Y
Y
R
R
L
L
L
L
H
H
740
|
D
D
A
A
R
R
P
P
K
K
E
E
G
G
D
D
D
D
R
R
750
|
P
P
F
F
F
F
W
W
L
L
F
F
E
E
N
N
V
V
V
V
760
|
A
A
M
M
G
G
V
V
S
S
D
D
K
K
R
R
D
D
I
I
770
|
S
S
R
R
F
F
L
L
E
E
S
S
N
N
P
P
V
V
M
M
780
|
I
I
D
D
A
A
K
K
E
E
V
V
S
S
A
A
A
A
H
H
790
|
R
R
A
A
R
R
Y
Y
F
F
W
W
G
G
N
N
L
L
P
P
800
|
G
G
M
M
N
N
R
R
P
P
L
L
A
A
S
S
T
T
V
V
810
|
N
N
D
D
K
K
L
L
E
E
L
L
Q
Q
E
E
C
C
L
L
820
|
E
E
H
H
G
G
R
R
I
I
A
A
K
K
F
F
S
S
K
K
830
|
V
V
R
R
T
T
I
I
T
T
T
T
R
R
S
S
N
N
S
S
840
|
I
I
K
K
Q
Q
G
G
K
K
D
D
Q
Q
H
H
F
F
P
P
850
|
V
V
F
F
M
M
N
N
E
E
K
K
E
E
D
D
I
I
L
L
860
|
W
W
C
C
T
T
E
E
M
M
E
E
R
R
V
V
F
F
G
G
870
|
F
F
P
P
V
V
H
H
Y
Y
T
T
D
D
V
V
S
S
N
N
880
|
M
M
S
S
R
H
L
L
A
A
R
R
Q
Q
R
R
L
L
L
L
890
|
G
G
R
R
S
S
W
W
S
S
V
V
P
P
V
V
I
I
R
R
900
|
H
H
L
L
F
F
A
A
P
P
L
L
K
K
E
E
Y
Y
F
F
910
|
A
A
C
C
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Bone marrow N.A.
In Vivo Model NOD/SCID mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.R882H (c.2645G>A) in gene DNMT3A cause the sensitivity of Idarubicin by unusual activation of pro-survival pathway
Ivosidenib
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: Oxalosuccinate decarboxylase (IDH1) [3]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug Ivosidenib
 Drug Info 
Molecule Alteration Missense mutation
p.R132H (c.395G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 6BKX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.88  Å
PDB: 4UMX
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.46
TM score: 0.85834
Amino acid change:
R132H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
S
S
K
K
K
K
I
I
S
S
G
G
G
G
S
S
10
|
V
V
V
V
E
E
M
M
Q
Q
G
G
D
D
E
E
M
M
T
T
20
|
R
R
I
I
I
I
W
W
E
E
L
L
I
I
K
K
E
E
K
K
30
|
L
L
I
I
F
F
P
P
Y
Y
V
V
E
E
L
L
D
D
L
L
40
|
H
H
S
S
Y
Y
D
D
L
L
G
G
I
I
E
E
N
N
R
R
50
|
D
D
A
A
T
T
N
N
D
D
Q
Q
V
V
T
T
K
K
D
D
60
|
A
A
A
A
E
E
A
A
I
I
K
K
K
K
H
H
N
N
V
V
70
|
G
G
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
80
|
E
E
K
K
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
90
|
Q
Q
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
100
|
R
R
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
110
|
E
E
A
A
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
120
|
L
L
V
V
S
S
G
G
W
W
V
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
R
H
H
H
A
A
Y
Y
G
G
D
D
Q
Q
Y
Y
140
|
R
R
A
A
T
T
D
D
F
F
V
V
V
V
P
P
G
G
P
P
150
|
G
G
K
K
V
V
E
E
I
I
T
T
Y
Y
T
T
P
P
S
S
160
|
D
D
G
G
T
T
Q
Q
K
K
V
V
T
T
Y
Y
L
L
V
V
170
|
H
H
N
N
F
F
E
E
E
E
G
G
G
G
G
G
V
V
A
A
180
|
M
M
G
G
M
M
Y
Y
N
N
Q
Q
D
D
K
K
S
S
I
I
190
|
E
E
D
D
F
F
A
A
H
H
S
S
S
S
F
F
Q
Q
M
M
200
|
A
A
L
L
S
S
K
K
G
G
W
W
P
P
L
L
Y
Y
L
L
210
|
S
S
T
T
K
K
N
N
T
T
I
I
L
L
K
K
K
K
Y
Y
220
|
D
D
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
230
|
I
I
Y
Y
D
D
K
K
Q
Q
Y
Y
K
K
S
S
Q
Q
F
F
240
|
E
E
A
A
Q
Q
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
250
|
L
L
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
A
A
M
M
260
|
K
K
S
S
E
E
G
G
G
G
F
F
I
I
W
W
A
A
C
C
270
|
K
K
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
280
|
S
S
V
V
A
A
Q
Q
G
G
Y
Y
G
G
S
S
L
L
G
G
290
|
M
M
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
300
|
G
G
K
K
T
T
V
V
E
E
A
A
E
E
A
A
A
A
H
H
310
|
G
G
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
M
M
Y
Y
320
|
Q
Q
K
K
G
G
Q
Q
E
E
T
T
S
S
T
T
N
N
P
P
330
|
I
I
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
340
|
L
L
A
A
H
H
R
R
A
A
K
K
L
L
D
D
N
N
N
N
350
|
K
K
E
E
L
L
A
A
F
F
F
F
A
A
N
N
A
A
L
L
360
|
E
E
E
E
V
V
S
S
I
I
E
E
T
T
I
I
E
E
A
A
370
|
G
G
F
F
M
M
T
T
K
K
D
D
L
L
A
A
A
A
C
C
380
|
I
I
K
K
G
G
L
L
P
P
N
N
V
V
Q
Q
R
R
S
S
390
|
D
D
Y
Y
L
L
N
N
T
T
F
F
E
E
F
F
M
M
D
D
400
|
K
K
L
L
G
G
E
E
N
N
L
L
K
K
I
I
K
K
L
L
410
|
A
A
Q
Q
A
A
K
K
L
L
S
S
L
L
E
E
H
H
H
H
420
|
H
H
H
H
H
H
H
H
H
H
H
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Oxalosuccinate decarboxylase (IDH1) [3]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug Ivosidenib
 Drug Info 
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6IO0
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.30204
Amino acid change:
R132C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
S
-
K
-
K
-
I
-
S
-
G
-
G
-
S
10
|
-
V
-
V
-
E
-
M
-
Q
-
G
-
D
-
E
-
M
-
T
20
|
-
R
-
I
-
I
-
W
-
E
-
L
-
I
-
K
-
E
-
K
30
|
-
L
-
I
-
F
-
P
-
Y
-
V
-
E
-
L
-
D
-
L
40
|
-
H
-
S
-
Y
-
D
-
L
-
G
-
I
-
E
-
N
-
R
50
|
-
D
-
A
-
T
-
N
-
D
-
Q
-
V
-
T
-
K
-
D
60
|
-
A
-
A
-
E
-
A
-
I
-
K
-
K
-
H
-
N
-
V
70
|
-
G
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
80
|
-
E
-
K
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
90
|
-
Q
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
100
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
110
|
-
E
-
A
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
120
|
-
L
-
V
-
S
-
G
-
W
-
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
S
C
H
H
A
A
Y
Y
G
G
D
D
-
Q
-
Y
140
|
-
R
-
A
-
T
-
D
-
F
-
V
-
V
-
P
-
G
-
P
150
|
-
G
-
K
-
V
-
E
-
I
-
T
-
Y
-
T
-
P
-
S
160
|
-
D
-
G
-
T
-
Q
-
K
-
V
-
T
-
Y
-
L
-
V
170
|
-
H
-
N
-
F
-
E
-
E
-
G
-
G
-
G
-
V
-
A
180
|
-
M
-
G
-
M
-
Y
-
N
-
Q
-
D
-
K
-
S
-
I
190
|
-
E
-
D
-
F
-
A
-
H
-
S
-
S
-
F
-
Q
-
M
200
|
-
A
-
L
-
S
-
K
-
G
-
W
-
P
-
L
-
Y
-
L
210
|
-
S
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
K
-
Y
220
|
-
D
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
230
|
-
I
-
Y
-
D
-
K
-
Q
-
Y
-
K
-
S
-
Q
-
F
240
|
-
E
-
A
-
Q
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
250
|
-
L
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
A
-
M
260
|
-
K
-
S
-
E
-
G
-
G
-
F
-
I
-
W
-
A
-
C
270
|
-
K
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
280
|
-
S
-
V
-
A
-
Q
-
G
-
Y
-
G
-
S
-
L
-
G
290
|
-
M
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
300
|
-
G
-
K
-
T
-
V
-
E
-
A
-
E
-
A
-
A
-
H
310
|
-
G
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
M
-
Y
320
|
-
Q
-
K
-
G
-
Q
-
E
-
T
-
S
-
T
-
N
-
P
330
|
-
I
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
340
|
-
L
-
A
-
H
-
R
-
A
-
K
-
L
-
D
-
N
-
N
350
|
-
K
-
E
-
L
-
A
-
F
-
F
-
A
-
N
-
A
-
L
360
|
-
E
-
E
-
V
-
S
-
I
-
E
-
T
-
I
-
E
-
A
370
|
-
G
-
F
-
M
-
T
-
K
-
D
-
L
-
A
-
A
-
C
380
|
-
I
-
K
-
G
-
L
-
P
-
N
-
V
-
Q
-
R
-
S
390
|
-
D
-
Y
-
L
-
N
-
T
-
F
-
E
-
F
-
M
-
D
400
|
-
K
-
L
-
G
-
E
-
N
-
L
-
K
-
I
-
K
-
L
410
|
-
A
-
Q
-
A
-
K
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mercaptopurine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytosolic purine 5'-nucleotidase (NT5C2) [4], [5]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Resistant Drug Mercaptopurine
 Drug Info 
Molecule Alteration Missense mutation
p.R238W (c.c712t)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-10
|
-
H
-
H
-
S
-
S
-
G
-
L
-
V
-
P
-
R
-
G
0
|
-
S
-
M
-
S
T
T
S
S
W
W
S
S
D
D
R
R
L
L
10
|
Q
Q
N
N
A
A
A
A
D
D
M
M
P
P
A
A
N
N
M
M
20
|
D
D
K
K
H
H
A
A
L
L
K
K
K
K
Y
Y
R
R
R
R
30
|
E
E
A
A
Y
Y
H
H
R
R
V
V
F
F
V
V
N
N
R
R
40
|
S
S
L
L
A
A
M
M
E
E
K
K
I
I
K
K
C
C
F
F
50
|
G
G
F
F
D
D
M
M
D
D
Y
Y
T
T
L
L
A
A
V
V
60
|
Y
Y
K
K
S
S
P
P
E
E
Y
Y
E
E
S
S
L
L
G
G
70
|
F
F
E
E
L
L
T
T
V
V
E
E
R
R
L
L
V
V
S
S
80
|
I
I
G
G
Y
Y
P
P
Q
Q
E
E
L
L
L
L
S
S
F
F
90
|
A
A
Y
Y
D
D
S
S
T
T
F
F
P
P
T
T
R
R
G
G
100
|
L
L
V
V
F
F
D
D
T
T
L
L
Y
Y
G
G
N
N
L
L
110
|
L
L
K
K
V
V
D
D
A
A
Y
Y
G
G
N
N
L
L
L
L
120
|
V
V
C
C
A
A
H
H
G
G
F
F
N
N
F
F
I
I
R
R
130
|
G
G
P
P
E
E
T
T
R
R
E
E
Q
Q
Y
Y
P
P
N
N
140
|
K
K
F
F
I
I
Q
Q
R
R
D
D
D
D
T
T
E
E
R
R
150
|
F
F
Y
Y
I
I
L
L
N
N
T
T
L
L
F
F
N
N
L
L
160
|
P
P
E
E
T
T
Y
Y
L
L
L
L
A
A
C
C
L
L
V
V
170
|
D
D
F
F
F
F
T
T
N
N
C
C
P
P
R
R
Y
Y
T
T
180
|
S
S
C
C
E
E
T
T
G
G
F
F
K
K
D
D
G
G
D
D
190
|
L
L
F
F
M
M
S
S
Y
Y
R
R
S
S
M
M
F
F
Q
Q
200
|
D
D
V
V
R
R
D
D
A
A
V
V
D
D
W
W
V
V
H
H
210
|
Y
Y
K
K
G
G
S
S
L
L
K
K
E
E
K
K
T
T
V
V
220
|
E
E
N
N
L
L
E
E
K
K
Y
Y
V
V
V
V
K
K
D
D
230
|
G
G
K
K
L
L
P
P
L
L
L
L
L
L
S
S
R
W
M
M
240
|
K
K
E
E
V
V
G
G
K
K
V
V
F
F
L
L
A
A
T
T
250
|
N
N
S
S
D
D
Y
Y
K
K
Y
Y
T
T
D
D
K
K
I
I
260
|
M
M
T
T
Y
Y
L
L
F
F
D
D
F
F
P
P
H
H
G
G
270
|
P
P
K
K
P
P
G
G
S
S
S
S
H
H
R
R
P
P
W
W
280
|
Q
Q
S
S
Y
Y
F
F
D
D
L
L
I
I
L
L
V
V
D
D
290
|
A
A
R
R
K
K
P
P
L
L
F
F
F
F
G
G
E
E
G
G
300
|
T
T
V
V
L
L
R
R
Q
Q
V
V
D
D
T
T
K
K
T
T
310
|
G
G
K
K
L
L
K
K
I
I
G
G
T
T
Y
Y
T
T
G
G
320
|
P
P
L
L
Q
Q
H
H
G
G
I
I
V
V
Y
Y
S
S
G
G
330
|
G
G
S
S
S
S
D
D
T
T
I
I
C
C
D
D
L
L
L
L
340
|
G
G
A
A
K
K
G
G
K
K
D
D
I
I
L
L
Y
Y
I
I
350
|
G
G
D
D
H
H
I
I
F
F
G
G
D
D
I
I
L
L
K
K
360
|
S
S
K
K
K
K
R
R
Q
Q
G
G
W
W
R
R
T
T
F
F
370
|
L
L
V
V
I
I
P
P
E
E
L
L
A
A
Q
Q
E
E
L
L
380
|
H
H
V
V
W
W
T
T
D
D
K
K
S
S
S
S
L
L
F
F
390
|
E
E
E
E
L
L
Q
Q
S
S
L
L
D
D
I
I
F
F
L
L
400
|
A
A
E
E
L
L
Y
Y
K
K
H
H
L
L
D
D
S
S
S
S
410
|
S
S
N
N
E
E
R
R
P
P
D
D
I
I
S
S
S
S
I
I
420
|
Q
Q
R
R
R
R
I
I
K
K
K
K
V
V
T
T
H
H
D
D
430
|
M
M
D
D
M
M
C
C
Y
Y
G
G
M
M
M
M
G
G
S
S
440
|
L
L
F
F
R
R
S
S
G
G
S
S
R
R
Q
Q
T
T
L
L
450
|
F
F
A
A
S
S
Q
Q
V
V
M
M
R
R
Y
Y
A
A
D
D
460
|
L
L
Y
Y
A
A
A
A
S
S
F
F
I
I
N
N
L
L
L
L
470
|
Y
Y
Y
Y
P
P
F
F
S
S
Y
Y
L
L
F
F
R
R
A
A
480
|
A
A
H
H
V
V
L
L
M
M
P
P
H
H
E
E
S
S
-
T
490
|
-
V
-
E
-
H
-
T
-
H
-
V
-
D
-
I
-
N
-
E
500
|
-
M
-
E
-
S
-
P
-
L
-
A
-
T
-
R
-
N
-
R
510
|
-
T
-
S
-
V
-
D
-
F
-
K
-
D
-
T
-
D
-
Y
520
|
-
K
-
R
-
H
-
Q
-
L
-
T
-
R
-
S
-
I
-
S
530
|
-
E
-
I
-
K
-
P
-
P
-
N
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).
Thioguanine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytosolic purine 5'-nucleotidase (NT5C2) [4], [5]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Resistant Drug Thioguanine
 Drug Info 
Molecule Alteration Missense mutation
p.R238W (c.c712t)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-10
|
-
H
-
H
-
S
-
S
-
G
-
L
-
V
-
P
-
R
-
G
0
|
-
S
-
M
-
S
T
T
S
S
W
W
S
S
D
D
R
R
L
L
10
|
Q
Q
N
N
A
A
A
A
D
D
M
M
P
P
A
A
N
N
M
M
20
|
D
D
K
K
H
H
A
A
L
L
K
K
K
K
Y
Y
R
R
R
R
30
|
E
E
A
A
Y
Y
H
H
R
R
V
V
F
F
V
V
N
N
R
R
40
|
S
S
L
L
A
A
M
M
E
E
K
K
I
I
K
K
C
C
F
F
50
|
G
G
F
F
D
D
M
M
D
D
Y
Y
T
T
L
L
A
A
V
V
60
|
Y
Y
K
K
S
S
P
P
E
E
Y
Y
E
E
S
S
L
L
G
G
70
|
F
F
E
E
L
L
T
T
V
V
E
E
R
R
L
L
V
V
S
S
80
|
I
I
G
G
Y
Y
P
P
Q
Q
E
E
L
L
L
L
S
S
F
F
90
|
A
A
Y
Y
D
D
S
S
T
T
F
F
P
P
T
T
R
R
G
G
100
|
L
L
V
V
F
F
D
D
T
T
L
L
Y
Y
G
G
N
N
L
L
110
|
L
L
K
K
V
V
D
D
A
A
Y
Y
G
G
N
N
L
L
L
L
120
|
V
V
C
C
A
A
H
H
G
G
F
F
N
N
F
F
I
I
R
R
130
|
G
G
P
P
E
E
T
T
R
R
E
E
Q
Q
Y
Y
P
P
N
N
140
|
K
K
F
F
I
I
Q
Q
R
R
D
D
D
D
T
T
E
E
R
R
150
|
F
F
Y
Y
I
I
L
L
N
N
T
T
L
L
F
F
N
N
L
L
160
|
P
P
E
E
T
T
Y
Y
L
L
L
L
A
A
C
C
L
L
V
V
170
|
D
D
F
F
F
F
T
T
N
N
C
C
P
P
R
R
Y
Y
T
T
180
|
S
S
C
C
E
E
T
T
G
G
F
F
K
K
D
D
G
G
D
D
190
|
L
L
F
F
M
M
S
S
Y
Y
R
R
S
S
M
M
F
F
Q
Q
200
|
D
D
V
V
R
R
D
D
A
A
V
V
D
D
W
W
V
V
H
H
210
|
Y
Y
K
K
G
G
S
S
L
L
K
K
E
E
K
K
T
T
V
V
220
|
E
E
N
N
L
L
E
E
K
K
Y
Y
V
V
V
V
K
K
D
D
230
|
G
G
K
K
L
L
P
P
L
L
L
L
L
L
S
S
R
W
M
M
240
|
K
K
E
E
V
V
G
G
K
K
V
V
F
F
L
L
A
A
T
T
250
|
N
N
S
S
D
D
Y
Y
K
K
Y
Y
T
T
D
D
K
K
I
I
260
|
M
M
T
T
Y
Y
L
L
F
F
D
D
F
F
P
P
H
H
G
G
270
|
P
P
K
K
P
P
G
G
S
S
S
S
H
H
R
R
P
P
W
W
280
|
Q
Q
S
S
Y
Y
F
F
D
D
L
L
I
I
L
L
V
V
D
D
290
|
A
A
R
R
K
K
P
P
L
L
F
F
F
F
G
G
E
E
G
G
300
|
T
T
V
V
L
L
R
R
Q
Q
V
V
D
D
T
T
K
K
T
T
310
|
G
G
K
K
L
L
K
K
I
I
G
G
T
T
Y
Y
T
T
G
G
320
|
P
P
L
L
Q
Q
H
H
G
G
I
I
V
V
Y
Y
S
S
G
G
330
|
G
G
S
S
S
S
D
D
T
T
I
I
C
C
D
D
L
L
L
L
340
|
G
G
A
A
K
K
G
G
K
K
D
D
I
I
L
L
Y
Y
I
I
350
|
G
G
D
D
H
H
I
I
F
F
G
G
D
D
I
I
L
L
K
K
360
|
S
S
K
K
K
K
R
R
Q
Q
G
G
W
W
R
R
T
T
F
F
370
|
L
L
V
V
I
I
P
P
E
E
L
L
A
A
Q
Q
E
E
L
L
380
|
H
H
V
V
W
W
T
T
D
D
K
K
S
S
S
S
L
L
F
F
390
|
E
E
E
E
L
L
Q
Q
S
S
L
L
D
D
I
I
F
F
L
L
400
|
A
A
E
E
L
L
Y
Y
K
K
H
H
L
L
D
D
S
S
S
S
410
|
S
S
N
N
E
E
R
R
P
P
D
D
I
I
S
S
S
S
I
I
420
|
Q
Q
R
R
R
R
I
I
K
K
K
K
V
V
T
T
H
H
D
D
430
|
M
M
D
D
M
M
C
C
Y
Y
G
G
M
M
M
M
G
G
S
S
440
|
L
L
F
F
R
R
S
S
G
G
S
S
R
R
Q
Q
T
T
L
L
450
|
F
F
A
A
S
S
Q
Q
V
V
M
M
R
R
Y
Y
A
A
D
D
460
|
L
L
Y
Y
A
A
A
A
S
S
F
F
I
I
N
N
L
L
L
L
470
|
Y
Y
Y
Y
P
P
F
F
S
S
Y
Y
L
L
F
F
R
R
A
A
480
|
A
A
H
H
V
V
L
L
M
M
P
P
H
H
E
E
S
S
-
T
490
|
-
V
-
E
-
H
-
T
-
H
-
V
-
D
-
I
-
N
-
E
500
|
-
M
-
E
-
S
-
P
-
L
-
A
-
T
-
R
-
N
-
R
510
|
-
T
-
S
-
V
-
D
-
F
-
K
-
D
-
T
-
D
-
Y
520
|
-
K
-
R
-
H
-
Q
-
L
-
T
-
R
-
S
-
I
-
S
530
|
-
E
-
I
-
K
-
P
-
P
-
N
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).
Clinical Trial Drug(s)
2 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) [6]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
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
-
40
|
-
A
-
D
-
K
-
R
-
I
-
K
-
V
-
A
-
K
-
P
50
|
-
V
-
V
-
E
-
M
-
D
-
G
-
D
-
E
-
M
-
T
60
|
-
R
-
I
-
I
-
W
-
Q
-
F
-
I
-
K
-
E
-
K
70
|
-
L
-
I
-
L
-
P
-
H
-
V
-
D
-
I
-
Q
-
L
80
|
-
K
-
Y
-
F
-
D
-
L
-
G
-
L
-
P
-
N
-
R
90
|
-
D
-
Q
-
T
-
D
-
D
-
Q
-
V
-
T
-
I
-
D
100
|
-
S
-
A
-
L
-
A
-
T
-
Q
-
K
-
Y
-
S
-
V
110
|
-
A
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
120
|
-
E
-
A
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
130
|
-
K
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
140
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
150
|
-
E
-
P
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
160
|
-
L
-
V
-
P
-
G
-
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
S
K
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
-
A
-
T
-
D
-
F
-
V
-
A
-
D
-
R
-
A
190
|
-
G
-
T
-
F
-
K
-
M
-
V
-
F
-
T
-
P
-
K
200
|
-
D
-
G
-
S
-
G
-
V
-
K
-
E
-
W
-
E
-
V
210
|
-
Y
-
N
-
F
-
P
-
A
-
G
-
G
-
V
-
G
-
M
220
|
-
G
-
M
-
Y
-
N
-
T
-
D
-
E
-
S
-
I
-
S
230
|
-
G
-
F
-
A
-
H
-
S
-
C
-
F
-
Q
-
Y
-
A
240
|
-
I
-
Q
-
K
-
K
-
W
-
P
-
L
-
Y
-
M
-
S
250
|
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
A
-
Y
-
D
260
|
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
-
I
270
|
-
F
-
D
-
K
-
H
-
Y
-
K
-
T
-
D
-
F
-
D
280
|
-
K
-
N
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
-
L
290
|
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
V
-
L
-
K
300
|
-
S
-
S
-
G
-
G
-
F
-
V
-
W
-
A
-
C
-
K
310
|
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
-
I
320
|
-
L
-
A
-
Q
-
G
-
F
-
G
-
S
-
L
-
G
-
L
330
|
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
-
G
340
|
-
K
-
T
-
I
-
E
-
A
-
E
-
A
-
A
-
H
-
G
350
|
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
E
-
H
-
Q
360
|
-
K
-
G
-
R
-
P
-
T
-
S
-
T
-
N
-
P
-
I
370
|
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
-
L
380
|
-
E
-
H
-
R
-
G
-
K
-
L
-
D
-
G
-
N
-
Q
390
|
-
D
-
L
-
I
-
R
-
F
-
A
-
Q
-
M
-
L
-
E
400
|
-
K
-
V
-
C
-
V
-
E
-
T
-
V
-
E
-
S
-
G
410
|
-
A
-
M
-
T
-
K
-
D
-
L
-
A
-
G
-
C
-
I
420
|
-
H
-
G
-
L
-
S
-
N
-
V
-
K
-
L
-
N
-
E
430
|
-
H
-
F
-
L
-
N
-
T
-
T
-
D
-
F
-
L
-
D
440
|
-
T
-
I
-
K
-
S
-
N
-
L
-
D
-
R
-
A
-
L
450
|
-
G
-
R
-
Q
-
S
-
L
-
E
-
H
-
H
-
H
-
H
460
|
-
H
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
In Vivo Model Acute myeloid leukemia xenograft mouse model Mus musculus
Experiment for
Drug Resistance		 IC50 assay
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [6]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug Enasidenib
 Drug Info 
Molecule Alteration Missense mutation
p.R140Q (c.419G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
Mutant Type Structure Method: X-ray diffraction Resolution: 1.54  Å
PDB: 5I95
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.33
TM score: 0.99798
Amino acid change:
R140Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
40
|
A
A
D
D
K
K
R
R
I
I
K
K
V
V
A
A
K
K
P
P
50
|
V
V
V
V
E
E
M
M
D
D
G
G
D
D
E
E
M
M
T
T
60
|
R
R
I
I
I
I
W
W
Q
Q
F
F
I
I
K
K
E
E
K
K
70
|
L
L
I
I
L
L
P
P
H
H
V
V
D
D
I
I
Q
Q
L
L
80
|
K
K
Y
Y
F
F
D
D
L
L
G
G
L
L
P
P
N
N
R
R
90
|
D
D
Q
Q
T
T
D
D
D
D
Q
Q
V
V
T
T
I
I
D
D
100
|
S
S
A
A
L
L
A
A
T
T
Q
Q
K
K
Y
Y
S
S
V
V
110
|
A
A
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
120
|
E
E
A
A
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
130
|
K
K
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
140
|
R
Q
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
150
|
E
E
P
P
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
160
|
L
L
V
V
P
P
G
G
W
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
K
R
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
A
A
T
T
D
D
F
F
V
V
A
A
D
D
R
R
A
A
190
|
G
G
T
T
F
F
K
K
M
M
V
V
F
F
T
T
P
P
K
K
200
|
D
D
G
G
S
S
G
G
V
V
K
K
E
E
W
W
E
E
V
V
210
|
Y
Y
N
N
F
F
P
P
A
A
G
G
G
G
V
V
G
G
M
M
220
|
G
G
M
M
Y
Y
N
N
T
T
D
D
E
E
S
S
I
I
S
S
230
|
G
G
F
F
A
A
H
H
S
S
C
C
F
F
Q
Q
Y
Y
A
A
240
|
I
I
Q
Q
K
K
K
K
W
W
P
P
L
L
Y
Y
M
M
S
S
250
|
T
T
K
K
N
N
T
T
I
I
L
L
K
K
A
A
Y
Y
D
D
260
|
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
I
I
270
|
F
F
D
D
K
K
H
H
Y
Y
K
K
T
T
D
D
F
F
D
D
280
|
K
K
N
N
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
L
L
290
|
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
V
V
L
L
K
K
300
|
S
S
S
S
G
G
G
G
F
F
V
V
W
W
A
A
C
C
K
K
310
|
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
I
I
320
|
L
L
A
A
Q
Q
G
G
F
F
G
G
S
S
L
L
G
G
L
L
330
|
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
G
G
340
|
K
K
T
T
I
I
E
E
A
A
E
E
A
A
A
A
H
H
G
G
350
|
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
E
E
H
H
Q
Q
360
|
K
K
G
G
R
R
P
P
T
T
S
S
T
T
N
N
P
P
I
I
370
|
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
L
L
380
|
E
E
H
H
R
R
G
G
K
K
L
L
D
D
G
G
N
N
Q
Q
390
|
D
D
L
L
I
I
R
R
F
F
A
A
Q
Q
M
M
L
L
E
E
400
|
K
K
V
V
C
C
V
V
E
E
T
T
V
V
E
E
S
S
G
G
410
|
A
A
M
M
T
T
K
K
D
D
L
L
A
A
G
G
C
C
I
I
420
|
H
H
G
G
L
L
S
S
N
N
V
V
K
K
L
L
N
N
E
E
430
|
H
H
F
F
L
L
N
N
T
T
T
T
D
D
F
F
L
L
D
D
440
|
T
T
I
I
K
K
S
S
N
N
L
L
D
D
R
R
A
A
L
L
450
|
G
G
R
R
Q
Q
S
L
L
E
E
H
H
H
H
H
H
H
H
H
460
|
H
H
H
H
H
H
H
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
In Vivo Model Acute myeloid leukemia xenograft mouse model Mus musculus
Experiment for
Drug Resistance		 IC50 assay
BAY1436032
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: Oxalosuccinate decarboxylase (IDH1) [7]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug BAY1436032
 Drug Info 
Molecule Alteration Missense mutation
p.R132H (c.395G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 6BKX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.88  Å
PDB: 4UMX
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.46
TM score: 0.85834
Amino acid change:
R132H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
S
S
K
K
K
K
I
I
S
S
G
G
G
G
S
S
10
|
V
V
V
V
E
E
M
M
Q
Q
G
G
D
D
E
E
M
M
T
T
20
|
R
R
I
I
I
I
W
W
E
E
L
L
I
I
K
K
E
E
K
K
30
|
L
L
I
I
F
F
P
P
Y
Y
V
V
E
E
L
L
D
D
L
L
40
|
H
H
S
S
Y
Y
D
D
L
L
G
G
I
I
E
E
N
N
R
R
50
|
D
D
A
A
T
T
N
N
D
D
Q
Q
V
V
T
T
K
K
D
D
60
|
A
A
A
A
E
E
A
A
I
I
K
K
K
K
H
H
N
N
V
V
70
|
G
G
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
80
|
E
E
K
K
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
90
|
Q
Q
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
100
|
R
R
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
110
|
E
E
A
A
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
120
|
L
L
V
V
S
S
G
G
W
W
V
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
R
H
H
H
A
A
Y
Y
G
G
D
D
Q
Q
Y
Y
140
|
R
R
A
A
T
T
D
D
F
F
V
V
V
V
P
P
G
G
P
P
150
|
G
G
K
K
V
V
E
E
I
I
T
T
Y
Y
T
T
P
P
S
S
160
|
D
D
G
G
T
T
Q
Q
K
K
V
V
T
T
Y
Y
L
L
V
V
170
|
H
H
N
N
F
F
E
E
E
E
G
G
G
G
G
G
V
V
A
A
180
|
M
M
G
G
M
M
Y
Y
N
N
Q
Q
D
D
K
K
S
S
I
I
190
|
E
E
D
D
F
F
A
A
H
H
S
S
S
S
F
F
Q
Q
M
M
200
|
A
A
L
L
S
S
K
K
G
G
W
W
P
P
L
L
Y
Y
L
L
210
|
S
S
T
T
K
K
N
N
T
T
I
I
L
L
K
K
K
K
Y
Y
220
|
D
D
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
230
|
I
I
Y
Y
D
D
K
K
Q
Q
Y
Y
K
K
S
S
Q
Q
F
F
240
|
E
E
A
A
Q
Q
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
250
|
L
L
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
A
A
M
M
260
|
K
K
S
S
E
E
G
G
G
G
F
F
I
I
W
W
A
A
C
C
270
|
K
K
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
280
|
S
S
V
V
A
A
Q
Q
G
G
Y
Y
G
G
S
S
L
L
G
G
290
|
M
M
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
300
|
G
G
K
K
T
T
V
V
E
E
A
A
E
E
A
A
A
A
H
H
310
|
G
G
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
M
M
Y
Y
320
|
Q
Q
K
K
G
G
Q
Q
E
E
T
T
S
S
T
T
N
N
P
P
330
|
I
I
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
340
|
L
L
A
A
H
H
R
R
A
A
K
K
L
L
D
D
N
N
N
N
350
|
K
K
E
E
L
L
A
A
F
F
F
F
A
A
N
N
A
A
L
L
360
|
E
E
E
E
V
V
S
S
I
I
E
E
T
T
I
I
E
E
A
A
370
|
G
G
F
F
M
M
T
T
K
K
D
D
L
L
A
A
A
A
C
C
380
|
I
I
K
K
G
G
L
L
P
P
N
N
V
V
Q
Q
R
R
S
S
390
|
D
D
Y
Y
L
L
N
N
T
T
F
F
E
E
F
F
M
M
D
D
400
|
K
K
L
L
G
G
E
E
N
N
L
L
K
K
I
I
K
K
L
L
410
|
A
A
Q
Q
A
A
K
K
L
L
S
S
L
L
E
E
H
H
H
H
420
|
H
H
H
H
H
H
H
H
H
H
H
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model HoxA9-IDH2R140Q cells N.A. N.A. N.A.
HoxA9-IDH2172K cells N.A. N.A. N.A.
HoxA9-IDH1R132H cells N.A. N.A. N.A.
HoxA9-IDH1R132C cells N.A. N.A. N.A.
In Vivo Model Mouse PDX model Mus musculus
Experiment for
Drug Resistance		 FACS assay
Mechanism Description BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.
Key Molecule: Oxalosuccinate decarboxylase (IDH1) [7]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug BAY1436032
 Drug Info 
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6IO0
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.30204
Amino acid change:
R132C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
S
-
K
-
K
-
I
-
S
-
G
-
G
-
S
10
|
-
V
-
V
-
E
-
M
-
Q
-
G
-
D
-
E
-
M
-
T
20
|
-
R
-
I
-
I
-
W
-
E
-
L
-
I
-
K
-
E
-
K
30
|
-
L
-
I
-
F
-
P
-
Y
-
V
-
E
-
L
-
D
-
L
40
|
-
H
-
S
-
Y
-
D
-
L
-
G
-
I
-
E
-
N
-
R
50
|
-
D
-
A
-
T
-
N
-
D
-
Q
-
V
-
T
-
K
-
D
60
|
-
A
-
A
-
E
-
A
-
I
-
K
-
K
-
H
-
N
-
V
70
|
-
G
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
80
|
-
E
-
K
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
90
|
-
Q
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
100
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
110
|
-
E
-
A
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
120
|
-
L
-
V
-
S
-
G
-
W
-
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
S
C
H
H
A
A
Y
Y
G
G
D
D
-
Q
-
Y
140
|
-
R
-
A
-
T
-
D
-
F
-
V
-
V
-
P
-
G
-
P
150
|
-
G
-
K
-
V
-
E
-
I
-
T
-
Y
-
T
-
P
-
S
160
|
-
D
-
G
-
T
-
Q
-
K
-
V
-
T
-
Y
-
L
-
V
170
|
-
H
-
N
-
F
-
E
-
E
-
G
-
G
-
G
-
V
-
A
180
|
-
M
-
G
-
M
-
Y
-
N
-
Q
-
D
-
K
-
S
-
I
190
|
-
E
-
D
-
F
-
A
-
H
-
S
-
S
-
F
-
Q
-
M
200
|
-
A
-
L
-
S
-
K
-
G
-
W
-
P
-
L
-
Y
-
L
210
|
-
S
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
K
-
Y
220
|
-
D
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
230
|
-
I
-
Y
-
D
-
K
-
Q
-
Y
-
K
-
S
-
Q
-
F
240
|
-
E
-
A
-
Q
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
250
|
-
L
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
A
-
M
260
|
-
K
-
S
-
E
-
G
-
G
-
F
-
I
-
W
-
A
-
C
270
|
-
K
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
280
|
-
S
-
V
-
A
-
Q
-
G
-
Y
-
G
-
S
-
L
-
G
290
|
-
M
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
300
|
-
G
-
K
-
T
-
V
-
E
-
A
-
E
-
A
-
A
-
H
310
|
-
G
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
M
-
Y
320
|
-
Q
-
K
-
G
-
Q
-
E
-
T
-
S
-
T
-
N
-
P
330
|
-
I
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
340
|
-
L
-
A
-
H
-
R
-
A
-
K
-
L
-
D
-
N
-
N
350
|
-
K
-
E
-
L
-
A
-
F
-
F
-
A
-
N
-
A
-
L
360
|
-
E
-
E
-
V
-
S
-
I
-
E
-
T
-
I
-
E
-
A
370
|
-
G
-
F
-
M
-
T
-
K
-
D
-
L
-
A
-
A
-
C
380
|
-
I
-
K
-
G
-
L
-
P
-
N
-
V
-
Q
-
R
-
S
390
|
-
D
-
Y
-
L
-
N
-
T
-
F
-
E
-
F
-
M
-
D
400
|
-
K
-
L
-
G
-
E
-
N
-
L
-
K
-
I
-
K
-
L
410
|
-
A
-
Q
-
A
-
K
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model HoxA9-IDH2R140Q cells N.A. N.A. N.A.
HoxA9-IDH2172K cells N.A. N.A. N.A.
HoxA9-IDH1R132H cells N.A. N.A. N.A.
HoxA9-IDH1R132C cells N.A. N.A. N.A.
In Vivo Model Mouse PDX model Mus musculus
Experiment for
Drug Resistance		 FACS assay
Mechanism Description BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.
Preclinical Drug(s)
5 drug(s) in total
Click to Show/Hide the Full List of Drugs
AGI-6780
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) [8]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug AGI-6780
 Drug Info 
Molecule Alteration Missense mutation
p.R140Q (c.419G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
Mutant Type Structure Method: X-ray diffraction Resolution: 1.54  Å
PDB: 5I95
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.33
TM score: 0.99798
Amino acid change:
R140Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
40
|
A
A
D
D
K
K
R
R
I
I
K
K
V
V
A
A
K
K
P
P
50
|
V
V
V
V
E
E
M
M
D
D
G
G
D
D
E
E
M
M
T
T
60
|
R
R
I
I
I
I
W
W
Q
Q
F
F
I
I
K
K
E
E
K
K
70
|
L
L
I
I
L
L
P
P
H
H
V
V
D
D
I
I
Q
Q
L
L
80
|
K
K
Y
Y
F
F
D
D
L
L
G
G
L
L
P
P
N
N
R
R
90
|
D
D
Q
Q
T
T
D
D
D
D
Q
Q
V
V
T
T
I
I
D
D
100
|
S
S
A
A
L
L
A
A
T
T
Q
Q
K
K
Y
Y
S
S
V
V
110
|
A
A
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
120
|
E
E
A
A
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
130
|
K
K
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
140
|
R
Q
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
150
|
E
E
P
P
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
160
|
L
L
V
V
P
P
G
G
W
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
K
R
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
A
A
T
T
D
D
F
F
V
V
A
A
D
D
R
R
A
A
190
|
G
G
T
T
F
F
K
K
M
M
V
V
F
F
T
T
P
P
K
K
200
|
D
D
G
G
S
S
G
G
V
V
K
K
E
E
W
W
E
E
V
V
210
|
Y
Y
N
N
F
F
P
P
A
A
G
G
G
G
V
V
G
G
M
M
220
|
G
G
M
M
Y
Y
N
N
T
T
D
D
E
E
S
S
I
I
S
S
230
|
G
G
F
F
A
A
H
H
S
S
C
C
F
F
Q
Q
Y
Y
A
A
240
|
I
I
Q
Q
K
K
K
K
W
W
P
P
L
L
Y
Y
M
M
S
S
250
|
T
T
K
K
N
N
T
T
I
I
L
L
K
K
A
A
Y
Y
D
D
260
|
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
I
I
270
|
F
F
D
D
K
K
H
H
Y
Y
K
K
T
T
D
D
F
F
D
D
280
|
K
K
N
N
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
L
L
290
|
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
V
V
L
L
K
K
300
|
S
S
S
S
G
G
G
G
F
F
V
V
W
W
A
A
C
C
K
K
310
|
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
I
I
320
|
L
L
A
A
Q
Q
G
G
F
F
G
G
S
S
L
L
G
G
L
L
330
|
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
G
G
340
|
K
K
T
T
I
I
E
E
A
A
E
E
A
A
A
A
H
H
G
G
350
|
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
E
E
H
H
Q
Q
360
|
K
K
G
G
R
R
P
P
T
T
S
S
T
T
N
N
P
P
I
I
370
|
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
L
L
380
|
E
E
H
H
R
R
G
G
K
K
L
L
D
D
G
G
N
N
Q
Q
390
|
D
D
L
L
I
I
R
R
F
F
A
A
Q
Q
M
M
L
L
E
E
400
|
K
K
V
V
C
C
V
V
E
E
T
T
V
V
E
E
S
S
G
G
410
|
A
A
M
M
T
T
K
K
D
D
L
L
A
A
G
G
C
C
I
I
420
|
H
H
G
G
L
L
S
S
N
N
V
V
K
K
L
L
N
N
E
E
430
|
H
H
F
F
L
L
N
N
T
T
T
T
D
D
F
F
L
L
D
D
440
|
T
T
I
I
K
K
S
S
N
N
L
L
D
D
R
R
A
A
L
L
450
|
G
G
R
R
Q
Q
S
L
L
E
E
H
H
H
H
H
H
H
H
H
460
|
H
H
H
H
H
H
H
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Blood N.A.
Mechanism Description The missense mutation p.R140Q (c.419G>A) in gene IDH2 cause the sensitivity of AGI-6780 by aberration of the drug's therapeutic target
Alpelisib/Binimetinib
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 Nras (NRAS) [9]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug Alpelisib/Binimetinib
 Drug Info 
Molecule Alteration Missense mutation
p.G12D (c.35G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 8JHL
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.55
TM score: 0.9318
Amino acid change:
G12D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
D
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
C
C
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
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NOMO1 cells Bone marrow Homo sapiens (Human) CVCL_1609
BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
THP1 cell Peripheral blood Homo sapiens (Human) CVCL_0006
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
BPTES
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: Oxalosuccinate decarboxylase (IDH1) [10]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug BPTES
 Drug Info 
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6IO0
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.30204
Amino acid change:
R132C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
S
-
K
-
K
-
I
-
S
-
G
-
G
-
S
10
|
-
V
-
V
-
E
-
M
-
Q
-
G
-
D
-
E
-
M
-
T
20
|
-
R
-
I
-
I
-
W
-
E
-
L
-
I
-
K
-
E
-
K
30
|
-
L
-
I
-
F
-
P
-
Y
-
V
-
E
-
L
-
D
-
L
40
|
-
H
-
S
-
Y
-
D
-
L
-
G
-
I
-
E
-
N
-
R
50
|
-
D
-
A
-
T
-
N
-
D
-
Q
-
V
-
T
-
K
-
D
60
|
-
A
-
A
-
E
-
A
-
I
-
K
-
K
-
H
-
N
-
V
70
|
-
G
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
80
|
-
E
-
K
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
90
|
-
Q
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
100
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
110
|
-
E
-
A
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
120
|
-
L
-
V
-
S
-
G
-
W
-
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
S
C
H
H
A
A
Y
Y
G
G
D
D
-
Q
-
Y
140
|
-
R
-
A
-
T
-
D
-
F
-
V
-
V
-
P
-
G
-
P
150
|
-
G
-
K
-
V
-
E
-
I
-
T
-
Y
-
T
-
P
-
S
160
|
-
D
-
G
-
T
-
Q
-
K
-
V
-
T
-
Y
-
L
-
V
170
|
-
H
-
N
-
F
-
E
-
E
-
G
-
G
-
G
-
V
-
A
180
|
-
M
-
G
-
M
-
Y
-
N
-
Q
-
D
-
K
-
S
-
I
190
|
-
E
-
D
-
F
-
A
-
H
-
S
-
S
-
F
-
Q
-
M
200
|
-
A
-
L
-
S
-
K
-
G
-
W
-
P
-
L
-
Y
-
L
210
|
-
S
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
K
-
Y
220
|
-
D
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
230
|
-
I
-
Y
-
D
-
K
-
Q
-
Y
-
K
-
S
-
Q
-
F
240
|
-
E
-
A
-
Q
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
250
|
-
L
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
A
-
M
260
|
-
K
-
S
-
E
-
G
-
G
-
F
-
I
-
W
-
A
-
C
270
|
-
K
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
280
|
-
S
-
V
-
A
-
Q
-
G
-
Y
-
G
-
S
-
L
-
G
290
|
-
M
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
300
|
-
G
-
K
-
T
-
V
-
E
-
A
-
E
-
A
-
A
-
H
310
|
-
G
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
M
-
Y
320
|
-
Q
-
K
-
G
-
Q
-
E
-
T
-
S
-
T
-
N
-
P
330
|
-
I
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
340
|
-
L
-
A
-
H
-
R
-
A
-
K
-
L
-
D
-
N
-
N
350
|
-
K
-
E
-
L
-
A
-
F
-
F
-
A
-
N
-
A
-
L
360
|
-
E
-
E
-
V
-
S
-
I
-
E
-
T
-
I
-
E
-
A
370
|
-
G
-
F
-
M
-
T
-
K
-
D
-
L
-
A
-
A
-
C
380
|
-
I
-
K
-
G
-
L
-
P
-
N
-
V
-
Q
-
R
-
S
390
|
-
D
-
Y
-
L
-
N
-
T
-
F
-
E
-
F
-
M
-
D
400
|
-
K
-
L
-
G
-
E
-
N
-
L
-
K
-
I
-
K
-
L
410
|
-
A
-
Q
-
A
-
K
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
AML cells N.A. Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 Manually cell counting assay
GSK321
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: Oxalosuccinate decarboxylase (IDH1) [11]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug GSK321
 Drug Info 
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6IO0
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.30204
Amino acid change:
R132C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
S
-
K
-
K
-
I
-
S
-
G
-
G
-
S
10
|
-
V
-
V
-
E
-
M
-
Q
-
G
-
D
-
E
-
M
-
T
20
|
-
R
-
I
-
I
-
W
-
E
-
L
-
I
-
K
-
E
-
K
30
|
-
L
-
I
-
F
-
P
-
Y
-
V
-
E
-
L
-
D
-
L
40
|
-
H
-
S
-
Y
-
D
-
L
-
G
-
I
-
E
-
N
-
R
50
|
-
D
-
A
-
T
-
N
-
D
-
Q
-
V
-
T
-
K
-
D
60
|
-
A
-
A
-
E
-
A
-
I
-
K
-
K
-
H
-
N
-
V
70
|
-
G
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
80
|
-
E
-
K
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
90
|
-
Q
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
100
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
110
|
-
E
-
A
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
120
|
-
L
-
V
-
S
-
G
-
W
-
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
S
C
H
H
A
A
Y
Y
G
G
D
D
-
Q
-
Y
140
|
-
R
-
A
-
T
-
D
-
F
-
V
-
V
-
P
-
G
-
P
150
|
-
G
-
K
-
V
-
E
-
I
-
T
-
Y
-
T
-
P
-
S
160
|
-
D
-
G
-
T
-
Q
-
K
-
V
-
T
-
Y
-
L
-
V
170
|
-
H
-
N
-
F
-
E
-
E
-
G
-
G
-
G
-
V
-
A
180
|
-
M
-
G
-
M
-
Y
-
N
-
Q
-
D
-
K
-
S
-
I
190
|
-
E
-
D
-
F
-
A
-
H
-
S
-
S
-
F
-
Q
-
M
200
|
-
A
-
L
-
S
-
K
-
G
-
W
-
P
-
L
-
Y
-
L
210
|
-
S
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
K
-
Y
220
|
-
D
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
230
|
-
I
-
Y
-
D
-
K
-
Q
-
Y
-
K
-
S
-
Q
-
F
240
|
-
E
-
A
-
Q
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
250
|
-
L
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
A
-
M
260
|
-
K
-
S
-
E
-
G
-
G
-
F
-
I
-
W
-
A
-
C
270
|
-
K
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
280
|
-
S
-
V
-
A
-
Q
-
G
-
Y
-
G
-
S
-
L
-
G
290
|
-
M
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
300
|
-
G
-
K
-
T
-
V
-
E
-
A
-
E
-
A
-
A
-
H
310
|
-
G
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
M
-
Y
320
|
-
Q
-
K
-
G
-
Q
-
E
-
T
-
S
-
T
-
N
-
P
330
|
-
I
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
340
|
-
L
-
A
-
H
-
R
-
A
-
K
-
L
-
D
-
N
-
N
350
|
-
K
-
E
-
L
-
A
-
F
-
F
-
A
-
N
-
A
-
L
360
|
-
E
-
E
-
V
-
S
-
I
-
E
-
T
-
I
-
E
-
A
370
|
-
G
-
F
-
M
-
T
-
K
-
D
-
L
-
A
-
A
-
C
380
|
-
I
-
K
-
G
-
L
-
P
-
N
-
V
-
Q
-
R
-
S
390
|
-
D
-
Y
-
L
-
N
-
T
-
F
-
E
-
F
-
M
-
D
400
|
-
K
-
L
-
G
-
E
-
N
-
L
-
K
-
I
-
K
-
L
410
|
-
A
-
Q
-
A
-
K
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model HT-1080 cells Acetabulum Homo sapiens (Human) CVCL_0317
In Vivo Model Male CD-1 xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Diaphorase/resazurin coupled assay; Colony formation assay
SHP099
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: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [12]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Resistant Drug SHP099
 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
-
0
|
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
|
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
|
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
|
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
|
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
|
S
S
Q
Q
S
S
H
H
P
P
G
G
D
D
F
F
V
V
L
L
150
|
S
S
V
V
R
R
T
T
G
G
D
D
D
D
K
K
G
G
E
E
160
|
S
S
N
N
D
D
G
G
K
K
S
S
K
K
V
V
T
T
H
H
170
|
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
|
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
|
E
E
F
F
E
E
T
T
L
L
Q
Q
Q
Q
Q
Q
E
E
C
C
260
|
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
|
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
|
V
V
E
E
R
R
G
G
K
K
S
S
K
K
C
C
V
V
K
K
370
|
Y
Y
W
W
P
P
D
D
E
E
Y
Y
A
A
L
L
K
K
E
E
380
|
Y
Y
G
G
V
V
M
M
R
R
V
V
R
R
N
N
V
V
K
K
390
|
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
|
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
|
E
E
E
E
V
V
H
H
H
H
K
K
Q
Q
E
E
S
S
I
I
450
|
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
|
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 Identified from the Human Clinical Data
In Vitro Model TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
Mechanism Description The SHP2 variant carrying the potent activating mutation E76K exhibits an open-state structure, which induces drastic domain reorganization to expose the active site and eliminate the binding pocket for the allosteric inhibitor SHP099.
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
IDH2 inhibitors
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) [13]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug IDH2 inhibitors
 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
-
40
|
-
A
-
D
-
K
-
R
-
I
-
K
-
V
-
A
-
K
-
P
50
|
-
V
-
V
-
E
-
M
-
D
-
G
-
D
-
E
-
M
-
T
60
|
-
R
-
I
-
I
-
W
-
Q
-
F
-
I
-
K
-
E
-
K
70
|
-
L
-
I
-
L
-
P
-
H
-
V
-
D
-
I
-
Q
-
L
80
|
-
K
-
Y
-
F
-
D
-
L
-
G
-
L
-
P
-
N
-
R
90
|
-
D
-
Q
-
T
-
D
-
D
-
Q
-
V
-
T
-
I
-
D
100
|
-
S
-
A
-
L
-
A
-
T
-
Q
-
K
-
Y
-
S
-
V
110
|
-
A
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
120
|
-
E
-
A
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
130
|
-
K
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
140
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
150
|
-
E
-
P
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
160
|
-
L
-
V
-
P
-
G
-
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
S
K
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
-
A
-
T
-
D
-
F
-
V
-
A
-
D
-
R
-
A
190
|
-
G
-
T
-
F
-
K
-
M
-
V
-
F
-
T
-
P
-
K
200
|
-
D
-
G
-
S
-
G
-
V
-
K
-
E
-
W
-
E
-
V
210
|
-
Y
-
N
-
F
-
P
-
A
-
G
-
G
-
V
-
G
-
M
220
|
-
G
-
M
-
Y
-
N
-
T
-
D
-
E
-
S
-
I
-
S
230
|
-
G
-
F
-
A
-
H
-
S
-
C
-
F
-
Q
-
Y
-
A
240
|
-
I
-
Q
-
K
-
K
-
W
-
P
-
L
-
Y
-
M
-
S
250
|
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
A
-
Y
-
D
260
|
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
-
I
270
|
-
F
-
D
-
K
-
H
-
Y
-
K
-
T
-
D
-
F
-
D
280
|
-
K
-
N
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
-
L
290
|
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
V
-
L
-
K
300
|
-
S
-
S
-
G
-
G
-
F
-
V
-
W
-
A
-
C
-
K
310
|
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
-
I
320
|
-
L
-
A
-
Q
-
G
-
F
-
G
-
S
-
L
-
G
-
L
330
|
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
-
G
340
|
-
K
-
T
-
I
-
E
-
A
-
E
-
A
-
A
-
H
-
G
350
|
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
E
-
H
-
Q
360
|
-
K
-
G
-
R
-
P
-
T
-
S
-
T
-
N
-
P
-
I
370
|
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
-
L
380
|
-
E
-
H
-
R
-
G
-
K
-
L
-
D
-
G
-
N
-
Q
390
|
-
D
-
L
-
I
-
R
-
F
-
A
-
Q
-
M
-
L
-
E
400
|
-
K
-
V
-
C
-
V
-
E
-
T
-
V
-
E
-
S
-
G
410
|
-
A
-
M
-
T
-
K
-
D
-
L
-
A
-
G
-
C
-
I
420
|
-
H
-
G
-
L
-
S
-
N
-
V
-
K
-
L
-
N
-
E
430
|
-
H
-
F
-
L
-
N
-
T
-
T
-
D
-
F
-
L
-
D
440
|
-
T
-
I
-
K
-
S
-
N
-
L
-
D
-
R
-
A
-
L
450
|
-
G
-
R
-
Q
-
S
-
L
-
E
-
H
-
H
-
H
-
H
460
|
-
H
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [13]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
Sensitive Drug IDH2 inhibitors
 Drug Info 
Molecule Alteration Missense mutation
p.R140Q (c.419G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
Mutant Type Structure Method: X-ray diffraction Resolution: 1.54  Å
PDB: 5I95
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.33
TM score: 0.99798
Amino acid change:
R140Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
40
|
A
A
D
D
K
K
R
R
I
I
K
K
V
V
A
A
K
K
P
P
50
|
V
V
V
V
E
E
M
M
D
D
G
G
D
D
E
E
M
M
T
T
60
|
R
R
I
I
I
I
W
W
Q
Q
F
F
I
I
K
K
E
E
K
K
70
|
L
L
I
I
L
L
P
P
H
H
V
V
D
D
I
I
Q
Q
L
L
80
|
K
K
Y
Y
F
F
D
D
L
L
G
G
L
L
P
P
N
N
R
R
90
|
D
D
Q
Q
T
T
D
D
D
D
Q
Q
V
V
T
T
I
I
D
D
100
|
S
S
A
A
L
L
A
A
T
T
Q
Q
K
K
Y
Y
S
S
V
V
110
|
A
A
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
120
|
E
E
A
A
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
130
|
K
K
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
140
|
R
Q
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
150
|
E
E
P
P
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
160
|
L
L
V
V
P
P
G
G
W
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
K
R
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
A
A
T
T
D
D
F
F
V
V
A
A
D
D
R
R
A
A
190
|
G
G
T
T
F
F
K
K
M
M
V
V
F
F
T
T
P
P
K
K
200
|
D
D
G
G
S
S
G
G
V
V
K
K
E
E
W
W
E
E
V
V
210
|
Y
Y
N
N
F
F
P
P
A
A
G
G
G
G
V
V
G
G
M
M
220
|
G
G
M
M
Y
Y
N
N
T
T
D
D
E
E
S
S
I
I
S
S
230
|
G
G
F
F
A
A
H
H
S
S
C
C
F
F
Q
Q
Y
Y
A
A
240
|
I
I
Q
Q
K
K
K
K
W
W
P
P
L
L
Y
Y
M
M
S
S
250
|
T
T
K
K
N
N
T
T
I
I
L
L
K
K
A
A
Y
Y
D
D
260
|
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
I
I
270
|
F
F
D
D
K
K
H
H
Y
Y
K
K
T
T
D
D
F
F
D
D
280
|
K
K
N
N
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
L
L
290
|
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
V
V
L
L
K
K
300
|
S
S
S
S
G
G
G
G
F
F
V
V
W
W
A
A
C
C
K
K
310
|
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
I
I
320
|
L
L
A
A
Q
Q
G
G
F
F
G
G
S
S
L
L
G
G
L
L
330
|
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
G
G
340
|
K
K
T
T
I
I
E
E
A
A
E
E
A
A
A
A
H
H
G
G
350
|
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
E
E
H
H
Q
Q
360
|
K
K
G
G
R
R
P
P
T
T
S
S
T
T
N
N
P
P
I
I
370
|
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
L
L
380
|
E
E
H
H
R
R
G
G
K
K
L
L
D
D
G
G
N
N
Q
Q
390
|
D
D
L
L
I
I
R
R
F
F
A
A
Q
Q
M
M
L
L
E
E
400
|
K
K
V
V
C
C
V
V
E
E
T
T
V
V
E
E
S
S
G
G
410
|
A
A
M
M
T
T
K
K
D
D
L
L
A
A
G
G
C
C
I
I
420
|
H
H
G
G
L
L
S
S
N
N
V
V
K
K
L
L
N
N
E
E
430
|
H
H
F
F
L
L
N
N
T
T
T
T
D
D
F
F
L
L
D
D
440
|
T
T
I
I
K
K
S
S
N
N
L
L
D
D
R
R
A
A
L
L
450
|
G
G
R
R
Q
Q
S
L
L
E
E
H
H
H
H
H
H
H
H
H
460
|
H
H
H
H
H
H
H
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
References
Ref 1 The role of mutations in epigenetic regulators in myeloid malignancies. Immunol Rev. 2015 Jan;263(1):22-35. doi: 10.1111/imr.12246.
Ref 2 Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin A single center experienceOncotarget. 2011 Nov;2(11):850-61. doi: 10.18632/oncotarget.347.
Ref 3 Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AMLN Engl J Med. 2018 Jun 21;378(25):2386-2398. doi: 10.1056/NEJMoa1716984. Epub 2018 Jun 2.
Ref 4 Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013 Mar;45(3):290-4. doi: 10.1038/ng.2558. Epub 2013 Feb 3.
Ref 5 The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-80. doi: 10.1182/asheducation-2014.1.174. Epub 2014 Nov 18.
Ref 6 Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemiaBlood. 2017 Aug 10;130(6):722-731. doi: 10.1182/blood-2017-04-779405. Epub 2017 Jun 6.
Ref 7 Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivoLeukemia. 2017 Oct;31(10):2020-2028. doi: 10.1038/leu.2017.46. Epub 2017 Jan 31.
Ref 8 Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiationScience. 2013 May 3;340(6132):622-6. doi: 10.1126/science.1234769. Epub 2013 Apr 4.
Ref 9 Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110AlphaJ Clin Invest. 2014 Apr;124(4):1794-809. doi: 10.1172/JCI69927. Epub 2014 Feb 24.
Ref 10 Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutationsExp Hematol. 2014 Apr;42(4):247-51. doi: 10.1016/j.exphem.2013.12.001. Epub 2013 Dec 11.
Ref 11 New IDH1 mutant inhibitors for treatment of acute myeloid leukemiaNat Chem Biol. 2015 Nov;11(11):878-86. doi: 10.1038/nchembio.1930. Epub 2015 Oct 5.
Ref 12 Selective inhibition of leukemia-associated SHP2(E69K) mutant by the allosteric SHP2 inhibitor SHP099Leukemia. 2018 May;32(5):1246-1249. doi: 10.1038/s41375-018-0020-5. Epub 2018 Jan 30.
Ref 13 Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: Preliminary results from KEYNOTE-0280.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.