Molecule Information

General Information of the Molecule (ID: Mol00819)
Name
BCR-ABL1 e8a2 variant (BCR-ABL1) ,Homo sapiens
Synonyms
BCR-ABL1; Fragment
    Click to Show/Hide
Molecule Type
Protein
Gene Name
BCR-ABL1
Sequence
QNSQQSFDSSSPPTPQCHKRHRHCPVVVSEATIVGVRKTGQIWPNDGEGAFHGDADGSFG
TPPGYGCAADRAEEQRRHQDGLPYIDDSPSSSPHLSSKGRGSRDALVSGALESTKASELD
LEKGLEMRKWVLSGILASEETYLSHLEALLLPMKPLKAAATTSQPVLTSQQIETIFFKVP
ELYEIHKEFYDGLFPRVQQWSHQQRVGDLFQKLASQLGVYRAFVDNYGVAMEMAEKCCQA
NAQFAEISENLRARSNKDAKDPTTKNSLETLLYKPVDRVTRSTLVLHDLLKHTPASHPDH
PLLQDALRISQNFLSSINEEITPRRQSMTVKKGELLNRKDKTTFEKLDYLMSKEDNYKRT
REYIRSLKMVPSIPYLEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALY
DFVASGDNTLSITKGEKLRVLGYNHNGE
    Click to Show/Hide
Uniprot ID
E7E8T7_HUMAN
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Ponatinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Relapsed acute lymphocytic leukemia [ICD-11: 2B33.5] [1]
Resistant Disease Relapsed acute lymphocytic leukemia [ICD-11: 2B33.5]
 Disease Info 
Resistant Drug Ponatinib
 Drug Info 
Molecule Alteration Missense mutation
p.T315I
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
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40
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90
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110
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140
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150
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A
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A
A
E
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Y
Y
L
L
160
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L
L
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S
S
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G
I
I
N
N
G
G
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F
F
L
L
170
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V
V
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R
E
E
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E
E
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180
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R
R
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L
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Y
E
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G
R
R
190
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V
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Y
H
H
Y
Y
R
R
I
I
N
N
T
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A
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S
200
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D
D
G
G
K
K
L
L
Y
Y
V
V
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S
S
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210
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R
R
F
F
N
N
T
T
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L
A
A
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E
L
L
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V
H
H
220
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H
H
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H
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A
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D
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I
230
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T
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L
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R
240
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N
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K
P
P
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T
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Y
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P
250
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D
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M
E
E
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T
260
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G
G
270
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G
G
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Q
Y
Y
G
G
E
E
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Y
Y
E
E
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G
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V
280
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W
W
K
K
K
K
Y
Y
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T
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290
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K
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E
E
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300
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E
E
E
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A
A
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M
310
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K
K
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E
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I
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P
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Q
320
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L
L
L
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330
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F
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I
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340
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G
N
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L
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L
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C
350
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N
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A
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L
L
360
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L
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Y
Y
M
M
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A
370
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M
M
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E
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L
L
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K
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I
380
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H
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390
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400
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490
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P
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H
510
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520
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L
L
530
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G
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Q
G
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H
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H
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540
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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
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.
Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]
Resistant Disease Chronic myeloid leukemia [ICD-11: 2A20.0]
 Disease Info 
Resistant Drug Ponatinib
 Drug Info 
Molecule Alteration Missense mutation
p.G250E
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
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150
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P
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N
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160
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170
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L
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L
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180
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S
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190
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R
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E
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S
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200
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S
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R
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R
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210
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Y
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H
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Y
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R
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N
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T
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D
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220
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G
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K
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L
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Y
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V
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S
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S
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R
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230
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F
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N
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T
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L
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A
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L
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H
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240
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H
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T
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250
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T
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L
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H
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P
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A
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P
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R
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N
-
260
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K
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P
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T
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V
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Y
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G
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V
-
S
S
P
P
N
N
270
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Y
Y
D
D
K
K
W
W
E
E
M
M
E
E
R
R
T
T
D
D
280
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I
I
T
T
M
M
K
K
H
H
K
K
L
L
G
G
G
E
G
G
290
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Q
Q
Y
Y
G
G
E
E
V
V
Y
Y
E
E
G
G
V
V
W
W
300
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K
K
K
K
Y
Y
S
S
L
L
T
T
V
V
A
A
V
V
K
K
310
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T
T
L
L
K
K
E
E
D
D
T
T
M
M
E
E
V
V
E
E
320
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E
E
F
F
L
L
K
K
E
E
A
A
A
A
V
V
M
L
K
K
330
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E
E
I
I
K
K
H
H
P
P
N
N
L
L
V
V
Q
Q
L
L
340
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L
L
G
G
V
V
C
C
T
T
R
R
E
E
P
P
P
P
F
F
350
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Y
Y
I
I
I
I
I
T
E
E
F
F
M
M
T
T
Y
Y
G
G
360
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N
N
L
L
L
L
D
D
Y
Y
L
L
R
R
E
E
C
C
N
N
370
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R
R
Q
Q
E
E
V
V
N
N
A
A
V
V
V
V
L
L
L
L
380
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Y
Y
M
M
A
A
T
T
Q
Q
I
I
S
S
S
S
A
A
M
M
390
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E
E
Y
Y
L
L
E
E
K
K
K
K
N
N
F
F
I
I
H
H
400
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R
R
N
D
L
L
A
A
A
A
R
R
N
N
C
C
L
L
V
V
410
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G
G
E
E
N
N
H
H
L
L
V
V
K
K
V
V
A
A
D
D
420
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F
F
G
G
L
L
S
S
R
R
L
L
M
M
T
Y
G
G
D
D
430
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T
T
Y
Y
T
T
A
A
H
H
A
A
G
G
A
A
K
K
F
F
440
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P
P
I
I
K
K
W
W
T
T
A
A
P
P
E
E
S
S
L
L
450
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A
A
Y
Y
N
N
K
K
F
F
S
S
I
I
K
K
S
S
D
D
460
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V
V
W
W
A
A
F
F
G
G
V
V
L
L
L
L
W
W
E
E
470
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I
I
A
A
T
T
Y
Y
G
G
M
M
S
S
P
P
Y
Y
P
P
480
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G
G
I
I
D
D
L
L
S
S
Q
Q
V
V
Y
Y
E
E
L
L
490
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L
L
E
E
K
K
D
D
Y
Y
R
R
M
M
E
E
R
R
P
P
500
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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.
References
Ref 1 Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29;367(22):2075-88. doi: 10.1056/NEJMoa1205127.

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