Drug Information

Drug (ID: DG00192) and It's Reported Resistant Information
Name
Ponatinib
Synonyms
Iclusig (TN)
    Click to Show/Hide
Indication
In total 1 Indication(s)
Mature B-cell lymphoma [ICD-11: 2A85]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Acute lymphocytic leukemia [ICD-11: 2B33]
[2]
Chronic myeloid leukemia [ICD-11: 2A20]
[2]
Target Fms-like tyrosine kinase 3 (FLT-3) FLT3_HUMAN [1]
Proto-oncogene c-Ret (RET) RET_HUMAN [1]
Tyrosine-protein kinase ABL1 (ABL) ABL1_HUMAN [1]
Tyrosine-protein kinase Kit (KIT) KIT_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C29H27F3N6O
IsoSMILES
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
InChI
1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
InChIKey
PHXJVRSECIGDHY-UHFFFAOYSA-N
PubChem CID
24826799
ChEBI ID
CHEBI:78543
TTD Drug ID
D0H0EQ
VARIDT ID
DR00204
DrugBank ID
DB08901
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Chronic myeloid leukemia [ICD-11: 2A20]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [2]
Resistant Disease Chronic myeloid leukemia [ICD-11: 2A20.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T315I
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.89  Å
PDB: 4XEY
Mutant Type Structure Method: X-ray diffraction Resolution: 2.17  Å
PDB: 5MO4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.69
TM score: 0.88225
Amino acid change:
T315I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
40
|
-
G
-
A
-
M
-
D
-
P
-
S
-
E
-
A
-
L
-
Q
50
|
-
R
-
P
-
V
-
A
-
S
-
D
-
F
-
E
-
P
-
Q
60
|
-
G
-
L
-
S
-
E
-
A
-
A
-
R
-
W
-
N
-
S
70
|
-
K
-
E
-
N
-
L
-
L
-
A
-
G
-
P
-
S
-
E
80
|
-
N
-
D
-
P
-
N
-
L
-
F
-
V
-
A
-
L
-
Y
90
|
-
D
-
F
-
V
-
A
-
S
-
G
-
D
-
N
-
T
-
L
100
|
-
S
-
I
-
T
-
K
-
G
-
E
-
K
-
L
-
R
-
V
110
|
-
L
-
G
-
Y
-
N
-
H
-
N
-
G
-
E
-
W
-
C
120
|
-
E
-
A
-
Q
-
T
-
K
-
N
-
G
-
Q
-
G
-
W
130
|
-
V
-
P
-
S
-
N
-
Y
M
I
A
T
S
P
V
V
N
N
140
|
S
S
L
L
E
E
K
K
H
H
S
S
W
W
Y
Y
H
H
G
G
150
|
P
P
V
V
S
S
R
R
N
N
A
A
A
A
E
E
Y
Y
L
L
160
|
L
L
S
S
S
S
G
G
I
I
N
N
G
G
S
S
F
F
L
L
170
|
V
V
R
R
E
E
S
S
E
E
S
S
S
S
P
P
G
G
Q
Q
180
|
R
R
S
S
I
I
S
S
L
L
R
R
Y
Y
E
E
G
G
R
R
190
|
V
V
Y
Y
H
H
Y
Y
R
R
I
I
N
N
T
T
A
A
S
S
200
|
D
D
G
G
K
K
L
L
Y
Y
V
V
S
S
S
S
E
E
S
S
210
|
R
R
F
F
N
N
T
T
L
L
A
A
E
E
L
L
V
V
H
H
220
|
H
H
H
H
S
S
T
T
V
V
A
A
D
D
G
G
L
L
I
I
230
|
T
T
T
T
L
L
H
H
Y
Y
P
P
A
A
P
P
K
K
R
R
240
|
N
N
K
K
P
P
T
T
V
V
Y
Y
G
G
V
V
S
S
P
P
250
|
N
N
Y
Y
D
D
K
K
W
W
E
E
M
M
E
E
R
R
T
T
260
|
D
D
I
I
T
T
M
M
K
K
H
H
K
K
L
L
G
G
G
G
270
|
G
G
Q
Q
Y
Y
G
G
E
E
V
V
Y
Y
E
E
G
G
V
V
280
|
W
W
K
K
K
K
Y
Y
S
S
L
L
T
T
V
V
A
A
V
V
290
|
K
K
T
T
L
L
K
K
E
E
D
D
T
T
M
M
E
E
V
V
300
|
E
E
E
E
F
F
L
L
K
K
E
E
A
A
A
A
V
V
M
M
310
|
K
K
E
E
I
I
K
K
H
H
P
P
N
N
L
L
V
V
Q
Q
320
|
L
L
L
L
G
G
V
V
C
C
T
T
R
R
E
E
P
P
P
P
330
|
F
F
Y
Y
I
I
I
I
T
I
E
E
F
F
M
M
T
T
Y
Y
340
|
G
G
N
N
L
L
L
L
D
D
Y
Y
L
L
R
R
E
E
C
C
350
|
N
N
R
R
Q
Q
E
E
V
V
N
N
A
A
V
V
V
V
L
L
360
|
L
L
Y
Y
M
M
A
A
T
T
Q
Q
I
I
S
S
S
S
A
A
370
|
M
M
E
E
Y
Y
L
L
E
E
K
K
K
K
N
N
F
F
I
I
380
|
H
H
R
R
D
N
L
L
A
A
A
A
R
R
N
N
C
C
L
L
390
|
V
V
G
G
E
E
N
N
H
H
L
L
V
V
K
K
V
V
A
A
400
|
D
D
F
F
G
G
L
L
S
S
R
R
L
L
M
M
T
T
G
G
410
|
D
D
T
T
Y
Y
T
T
A
A
H
H
A
A
G
G
A
A
K
K
420
|
F
F
P
P
I
I
K
K
W
W
T
T
A
A
P
P
E
E
S
S
430
|
L
L
A
A
Y
Y
N
N
K
K
F
F
S
S
I
I
K
K
S
S
440
|
D
D
V
V
W
W
A
A
F
F
G
G
V
V
L
L
L
L
W
W
450
|
E
E
I
I
A
A
T
T
Y
Y
G
G
M
M
S
S
P
P
Y
Y
460
|
P
P
G
G
I
I
D
D
L
L
S
S
Q
Q
V
V
Y
Y
E
E
470
|
L
L
L
L
E
E
K
K
D
D
Y
Y
R
R
M
M
E
E
R
R
480
|
P
P
E
E
G
G
C
C
P
P
E
E
K
K
V
V
Y
Y
E
E
490
|
L
L
M
M
R
R
A
A
C
C
W
W
Q
Q
W
W
N
N
P
P
500
|
S
S
D
D
R
R
P
P
S
S
F
F
A
A
E
E
I
I
H
H
510
|
Q
Q
A
A
F
F
E
E
T
T
M
M
F
F
Q
Q
E
E
S
S
520
|
S
S
I
I
S
S
D
D
E
E
V
V
E
E
K
K
E
E
L
L
530
|
G
G
K
K
Q
Q
G
G
V
V
L
-
E
-
H
-
H
-
H
-
540
|
H
-
H
-
H
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Sanger sequencing assay
Mechanism Description Ponatinib was highly active in heavily pretreated patients with Ph-positive leukemias with resistance to tyrosine kinase inhibitors, including patients with the BCR-ABL T315I mutation, other mutations, or no mutations.
Key Molecule: BCR-ABL1 e8a2 variant (BCR-ABL1) [2]
Resistant Disease Chronic myeloid leukemia [ICD-11: 2A20.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G250E
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.17  Å
PDB: 5MO4
Mutant Type Structure Method: Solution NMR Resolution: N.A.
PDB: 6XRG
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.4
TM score: 0.79586
Amino acid change:
G250E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
60
|
A
-
M
-
D
-
P
-
S
-
E
-
A
-
L
-
Q
-
R
-
70
|
P
-
V
-
A
-
S
-
D
-
F
-
E
-
P
-
Q
-
G
-
80
|
L
-
S
-
E
-
A
-
A
-
R
-
W
-
N
-
S
-
K
-
90
|
E
-
N
-
L
-
L
-
A
-
G
-
P
-
S
-
E
-
N
-
100
|
D
-
P
-
N
-
L
-
F
-
V
-
A
-
L
-
Y
-
D
-
110
|
F
-
V
-
A
-
S
-
G
-
D
-
N
-
T
-
L
-
S
-
120
|
I
-
T
-
K
-
G
-
E
-
K
-
L
-
R
-
V
-
L
-
130
|
G
-
Y
-
N
-
H
-
N
-
G
-
E
-
W
-
C
-
E
-
140
|
A
-
Q
-
T
-
K
-
N
-
G
-
Q
-
G
-
W
-
V
-
150
|
P
-
S
-
N
-
Y
-
I
-
T
-
P
-
V
-
N
-
S
-
160
|
L
-
E
-
K
-
H
-
S
-
W
-
Y
-
H
-
G
-
P
-
170
|
V
-
S
-
R
-
N
-
A
-
A
-
E
-
Y
-
L
-
L
-
180
|
S
-
S
-
G
-
I
-
N
-
G
-
S
-
F
-
L
-
V
-
190
|
R
-
E
-
S
-
E
-
S
-
S
-
P
-
G
-
Q
-
R
-
200
|
S
-
I
-
S
-
L
-
R
-
Y
-
E
-
G
-
R
-
V
-
210
|
Y
-
H
-
Y
-
R
-
I
-
N
-
T
-
A
-
S
-
D
-
220
|
G
-
K
-
L
-
Y
-
V
-
S
-
S
-
E
-
S
-
R
-
230
|
F
-
N
-
T
-
L
-
A
-
E
-
L
-
V
-
H
-
H
-
240
|
H
-
S
-
T
-
V
-
A
-
D
-
G
-
L
-
I
-
T
-
250
|
T
-
L
-
H
-
Y
-
P
-
A
-
P
-
K
-
R
-
N
-
260
|
K
-
P
-
T
-
V
-
Y
-
G
-
V
-
S
S
P
P
N
N
270
|
Y
Y
D
D
K
K
W
W
E
E
M
M
E
E
R
R
T
T
D
D
280
|
I
I
T
T
M
M
K
K
H
H
K
K
L
L
G
G
G
E
G
G
290
|
Q
Q
Y
Y
G
G
E
E
V
V
Y
Y
E
E
G
G
V
V
W
W
300
|
K
K
K
K
Y
Y
S
S
L
L
T
T
V
V
A
A
V
V
K
K
310
|
T
T
L
L
K
K
E
E
D
D
T
T
M
M
E
E
V
V
E
E
320
|
E
E
F
F
L
L
K
K
E
E
A
A
A
A
V
V
M
L
K
K
330
|
E
E
I
I
K
K
H
H
P
P
N
N
L
L
V
V
Q
Q
L
L
340
|
L
L
G
G
V
V
C
C
T
T
R
R
E
E
P
P
P
P
F
F
350
|
Y
Y
I
I
I
I
I
T
E
E
F
F
M
M
T
T
Y
Y
G
G
360
|
N
N
L
L
L
L
D
D
Y
Y
L
L
R
R
E
E
C
C
N
N
370
|
R
R
Q
Q
E
E
V
V
N
N
A
A
V
V
V
V
L
L
L
L
380
|
Y
Y
M
M
A
A
T
T
Q
Q
I
I
S
S
S
S
A
A
M
M
390
|
E
E
Y
Y
L
L
E
E
K
K
K
K
N
N
F
F
I
I
H
H
400
|
R
R
N
D
L
L
A
A
A
A
R
R
N
N
C
C
L
L
V
V
410
|
G
G
E
E
N
N
H
H
L
L
V
V
K
K
V
V
A
A
D
D
420
|
F
F
G
G
L
L
S
S
R
R
L
L
M
M
T
Y
G
G
D
D
430
|
T
T
Y
Y
T
T
A
A
H
H
A
A
G
G
A
A
K
K
F
F
440
|
P
P
I
I
K
K
W
W
T
T
A
A
P
P
E
E
S
S
L
L
450
|
A
A
Y
Y
N
N
K
K
F
F
S
S
I
I
K
K
S
S
D
D
460
|
V
V
W
W
A
A
F
F
G
G
V
V
L
L
L
L
W
W
E
E
470
|
I
I
A
A
T
T
Y
Y
G
G
M
M
S
S
P
P
Y
Y
P
P
480
|
G
G
I
I
D
D
L
L
S
S
Q
Q
V
V
Y
Y
E
E
L
L
490
|
L
L
E
E
K
K
D
D
Y
Y
R
R
M
M
E
E
R
R
P
P
500
|
E
E
G
G
C
C
P
P
E
E
K
K
V
V
Y
Y
E
E
L
L
510
|
M
M
R
R
A
A
C
C
W
W
Q
Q
W
W
N
N
P
P
S
S
520
|
D
D
R
R
P
P
S
S
F
F
A
A
E
E
I
I
H
H
Q
Q
530
|
A
A
F
F
E
E
T
T
M
M
F
F
Q
Q
E
E
S
S
S
S
540
|
I
I
S
S
D
D
E
E
V
V
E
E
K
K
E
E
L
L
G
G
550
|
K
K
Q
Q
G
G
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Sanger sequencing assay
Mechanism Description Ponatinib was highly active in heavily pretreated patients with Ph-positive leukemias with resistance to tyrosine kinase inhibitors, including patients with the BCR-ABL T315I mutation, other mutations, or no mutations.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [3], [4]
Resistant Disease Chronic myeloid leukemia [ICD-11: 2A20.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G12V
 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 Identified from the Human Clinical Data
Cell Pathway Regulation JAKT2/STAT signaling pathway Activation hsa04030
RAF/KRAS/MEK signaling pathway Activation hsa04010
In Vitro Model HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
U937 cells Blood Homo sapiens (Human) CVCL_0007
K562 cells Blood Homo sapiens (Human) CVCL_0004
KCL-22 cells Bone marrow Homo sapiens (Human) CVCL_2091
Sup-B15 cells Bone marrow Homo sapiens (Human) CVCL_0103
HEL cells Blood Homo sapiens (Human) CVCL_0001
HMC-1.2 cells Blood Homo sapiens (Human) CVCL_H205
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Sanger Sequencing assay
Mechanism Description This mutation is well known for its effects on proliferation and its association with AML and MPN, suggesting that this variant might have been involved in the TkI resistance of this patient.
Acute lymphocytic leukemia [ICD-11: 2B33]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: BCR-ABL1 e8a2 variant (BCR-ABL1) [2]
Resistant Disease Relapsed acute lymphocytic leukemia [ICD-11: 2B33.5]
 Disease Info 
Molecule Alteration Missense mutation
p.T315I
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.89  Å
PDB: 4XEY
Mutant Type Structure Method: X-ray diffraction Resolution: 2.17  Å
PDB: 5MO4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.69
TM score: 0.88225
Amino acid change:
T315I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
40
|
-
G
-
A
-
M
-
D
-
P
-
S
-
E
-
A
-
L
-
Q
50
|
-
R
-
P
-
V
-
A
-
S
-
D
-
F
-
E
-
P
-
Q
60
|
-
G
-
L
-
S
-
E
-
A
-
A
-
R
-
W
-
N
-
S
70
|
-
K
-
E
-
N
-
L
-
L
-
A
-
G
-
P
-
S
-
E
80
|
-
N
-
D
-
P
-
N
-
L
-
F
-
V
-
A
-
L
-
Y
90
|
-
D
-
F
-
V
-
A
-
S
-
G
-
D
-
N
-
T
-
L
100
|
-
S
-
I
-
T
-
K
-
G
-
E
-
K
-
L
-
R
-
V
110
|
-
L
-
G
-
Y
-
N
-
H
-
N
-
G
-
E
-
W
-
C
120
|
-
E
-
A
-
Q
-
T
-
K
-
N
-
G
-
Q
-
G
-
W
130
|
-
V
-
P
-
S
-
N
-
Y
M
I
A
T
S
P
V
V
N
N
140
|
S
S
L
L
E
E
K
K
H
H
S
S
W
W
Y
Y
H
H
G
G
150
|
P
P
V
V
S
S
R
R
N
N
A
A
A
A
E
E
Y
Y
L
L
160
|
L
L
S
S
S
S
G
G
I
I
N
N
G
G
S
S
F
F
L
L
170
|
V
V
R
R
E
E
S
S
E
E
S
S
S
S
P
P
G
G
Q
Q
180
|
R
R
S
S
I
I
S
S
L
L
R
R
Y
Y
E
E
G
G
R
R
190
|
V
V
Y
Y
H
H
Y
Y
R
R
I
I
N
N
T
T
A
A
S
S
200
|
D
D
G
G
K
K
L
L
Y
Y
V
V
S
S
S
S
E
E
S
S
210
|
R
R
F
F
N
N
T
T
L
L
A
A
E
E
L
L
V
V
H
H
220
|
H
H
H
H
S
S
T
T
V
V
A
A
D
D
G
G
L
L
I
I
230
|
T
T
T
T
L
L
H
H
Y
Y
P
P
A
A
P
P
K
K
R
R
240
|
N
N
K
K
P
P
T
T
V
V
Y
Y
G
G
V
V
S
S
P
P
250
|
N
N
Y
Y
D
D
K
K
W
W
E
E
M
M
E
E
R
R
T
T
260
|
D
D
I
I
T
T
M
M
K
K
H
H
K
K
L
L
G
G
G
G
270
|
G
G
Q
Q
Y
Y
G
G
E
E
V
V
Y
Y
E
E
G
G
V
V
280
|
W
W
K
K
K
K
Y
Y
S
S
L
L
T
T
V
V
A
A
V
V
290
|
K
K
T
T
L
L
K
K
E
E
D
D
T
T
M
M
E
E
V
V
300
|
E
E
E
E
F
F
L
L
K
K
E
E
A
A
A
A
V
V
M
M
310
|
K
K
E
E
I
I
K
K
H
H
P
P
N
N
L
L
V
V
Q
Q
320
|
L
L
L
L
G
G
V
V
C
C
T
T
R
R
E
E
P
P
P
P
330
|
F
F
Y
Y
I
I
I
I
T
I
E
E
F
F
M
M
T
T
Y
Y
340
|
G
G
N
N
L
L
L
L
D
D
Y
Y
L
L
R
R
E
E
C
C
350
|
N
N
R
R
Q
Q
E
E
V
V
N
N
A
A
V
V
V
V
L
L
360
|
L
L
Y
Y
M
M
A
A
T
T
Q
Q
I
I
S
S
S
S
A
A
370
|
M
M
E
E
Y
Y
L
L
E
E
K
K
K
K
N
N
F
F
I
I
380
|
H
H
R
R
D
N
L
L
A
A
A
A
R
R
N
N
C
C
L
L
390
|
V
V
G
G
E
E
N
N
H
H
L
L
V
V
K
K
V
V
A
A
400
|
D
D
F
F
G
G
L
L
S
S
R
R
L
L
M
M
T
T
G
G
410
|
D
D
T
T
Y
Y
T
T
A
A
H
H
A
A
G
G
A
A
K
K
420
|
F
F
P
P
I
I
K
K
W
W
T
T
A
A
P
P
E
E
S
S
430
|
L
L
A
A
Y
Y
N
N
K
K
F
F
S
S
I
I
K
K
S
S
440
|
D
D
V
V
W
W
A
A
F
F
G
G
V
V
L
L
L
L
W
W
450
|
E
E
I
I
A
A
T
T
Y
Y
G
G
M
M
S
S
P
P
Y
Y
460
|
P
P
G
G
I
I
D
D
L
L
S
S
Q
Q
V
V
Y
Y
E
E
470
|
L
L
L
L
E
E
K
K
D
D
Y
Y
R
R
M
M
E
E
R
R
480
|
P
P
E
E
G
G
C
C
P
P
E
E
K
K
V
V
Y
Y
E
E
490
|
L
L
M
M
R
R
A
A
C
C
W
W
Q
Q
W
W
N
N
P
P
500
|
S
S
D
D
R
R
P
P
S
S
F
F
A
A
E
E
I
I
H
H
510
|
Q
Q
A
A
F
F
E
E
T
T
M
M
F
F
Q
Q
E
E
S
S
520
|
S
S
I
I
S
S
D
D
E
E
V
V
E
E
K
K
E
E
L
L
530
|
G
G
K
K
Q
Q
G
G
V
V
L
-
E
-
H
-
H
-
H
-
540
|
H
-
H
-
H
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Sanger sequencing assay
Mechanism Description Ponatinib was highly active in heavily pretreated patients with Ph-positive leukemias with resistance to tyrosine kinase inhibitors, including patients with the BCR-ABL T315I mutation, other mutations, or no mutations.
References
Ref 1 Deregulated expression of miR-29a-3p, miR-494-3p and miR-660-5p affects sensitivity to tyrosine kinase inhibitors in CML leukemic stem cells. Oncotarget. 2017 Jul 25;8(30):49451-49469. doi: 10.18632/oncotarget.17706.
Ref 2 Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29;367(22):2075-88. doi: 10.1056/NEJMoa1205127.
Ref 3 European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013 Aug 8;122(6):872-84. doi: 10.1182/blood-2013-05-501569. Epub 2013 Jun 26.
Ref 4 Dissecting Genomic Aberrations in Myeloproliferative Neoplasms by Multiplex-PCR and Next Generation Sequencing. PLoS One. 2015 Apr 20;10(4):e0123476. doi: 10.1371/journal.pone.0123476. eCollection 2015.

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