Drug Information

Drug (ID: DG01737) and It's Reported Resistant Information
Name
APR-246/Cisplatin
Synonyms
APR-246/Cisplatin
    Click to Show/Hide
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  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
Lung cancer [ICD-11: 2C25]
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: Cellular tumor antigen p53 (TP53) [1]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y163C (c.488A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 8QWL
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.52
TM score: 0.99068
Amino acid change:
Y163C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
S
S
S
S
S
S
V
V
P
P
S
S
100
|
Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
|
R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
|
K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
|
L
L
N
N
K
K
M
L
F
F
C
C
Q
Q
L
L
A
A
K
K
140
|
T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
|
T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
|
M
M
A
A
I
I
Y
C
K
K
Q
Q
S
S
Q
Q
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
|
E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
|
P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
|
N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
|
N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
|
Y
Y
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
|
T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
|
S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
|
P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
|
S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
D
S
S
270
|
F
F
E
E
V
V
R
R
V
V
C
C
A
A
C
C
P
P
G
G
280
|
R
R
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
|
R
R
K
K
K
K
G
G
E
E
P
P
H
H
H
H
E
E
L
L
300
|
P
P
P
P
G
G
S
S
T
T
K
K
R
R
A
A
L
L
P
P
310
|
N
N
N
N
T
T
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R273H (c.818G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 2BIM
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.49
TM score: 0.9915
Amino acid change:
R273H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
S
S
S
S
S
S
V
V
P
P
S
S
100
|
Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
|
R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
|
K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
|
L
L
N
N
K
K
M
L
F
F
C
C
Q
Q
L
L
A
A
K
K
140
|
T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
|
T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
|
M
M
A
A
I
I
Y
Y
K
K
Q
Q
S
S
Q
Q
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
|
E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
|
P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
|
N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
|
N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
|
Y
Y
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
|
T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
|
S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
|
P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
|
S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
D
S
S
270
|
F
F
E
E
V
V
R
H
V
V
C
C
A
A
C
C
P
P
G
G
280
|
R
R
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
|
R
R
K
K
K
K
G
G
E
E
P
P
H
H
H
H
E
E
L
L
300
|
P
P
P
P
G
G
S
S
T
T
K
K
R
R
A
A
L
L
P
P
310
|
N
N
N
N
T
T
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Cellular tumor antigen p53 (TP53) [2]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.00  Å
PDB: 6FF9
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.29
TM score: 0.99711
Amino acid change:
R280K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
S
-
S
-
S
-
V
V
P
P
S
S
100
|
Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
|
R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
|
K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
|
L
L
N
N
K
K
M
M
F
F
C
C
Q
Q
L
L
A
A
K
K
140
|
T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
|
T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
|
M
M
A
A
I
I
Y
Y
K
K
Q
Q
S
S
Q
Q
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
|
E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
|
P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
|
N
N
L
L
R
R
V
V
E
E
Y
Y
L
L
D
D
D
D
R
R
210
|
N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
|
Y
Y
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
|
T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
N
240
|
S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
|
P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
|
S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
N
S
S
270
|
F
F
E
E
V
V
R
R
V
V
C
C
A
A
C
C
P
P
G
G
280
|
R
K
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
|
R
-
K
-
K
-
G
-
E
-
P
-
H
-
H
-
E
-
L
-
300
|
P
-
P
-
G
-
S
-
T
-
K
-
R
-
A
-
L
-
P
-
310
|
N
-
N
-
T
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 FMCA assay
References
Ref 1 APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cellsCell Death Dis. 2015 Jun 18;6(6):e1794. doi: 10.1038/cddis.2015.143.
Ref 2 Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancerJ Ovarian Res. 2016 May 14;9(1):27. doi: 10.1186/s13048-016-0239-6.

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