Molecule Information

General Information of the Molecule (ID: Mol00050)
Name
Cellular tumor antigen p53 (TP53) ,Homo sapiens
Synonyms
Antigen NY-CO-13; Phosphoprotein p53; Tumor suppressor p53; P53
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Molecule Type
Protein
Gene Name
TP53
Gene ID
7157
Location
chr17:7661779-7687538[-]
Sequence
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK
SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE
RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS
SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP
PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG
GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
    Click to Show/Hide
3D-structure
PDB ID
7XZZ
Classification
Gene regulation/dna
Method
Electron microscopy
Resolution
4.07  Å
Function
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.
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Uniprot ID
P53_HUMAN
Ensembl ID
ENSG00000141510
HGNC ID
HGNC:11998
        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
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Gefitinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung cancer [ICD-11: 2C25.5] [1]
Resistant Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Resistant Drug Gefitinib
 Drug Info 
Molecule Alteration Missense mutation
p.Y163C
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
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S
S
S
S
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V
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P
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100
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Q
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G
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G
G
F
F
110
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R
R
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L
G
G
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F
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L
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G
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A
120
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K
K
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C
C
T
T
Y
Y
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P
A
A
130
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L
L
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N
K
K
M
L
F
F
C
C
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L
L
A
A
K
K
140
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T
T
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C
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V
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L
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W
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D
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150
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T
T
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P
P
P
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P
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G
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T
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R
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R
A
A
160
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M
M
A
A
I
I
Y
C
K
K
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S
Q
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H
H
M
M
170
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T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
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E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
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P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
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N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
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N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
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Y
Y
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
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T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
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S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
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P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
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S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
D
S
S
270
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F
F
E
E
V
V
R
R
V
V
C
C
A
A
C
C
P
P
G
G
280
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R
R
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
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R
R
K
K
K
K
G
G
E
E
P
P
H
H
H
H
E
E
L
L
300
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P
P
P
P
G
G
S
S
T
T
K
K
R
R
A
A
L
L
P
P
310
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N
N
N
N
T
T
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation AXLK signaling pathway Activation hsa01521
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
Clinical Trial Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
Ganetespib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [2]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
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T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [2]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
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
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S
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S
-
S
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V
V
P
P
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100
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Q
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K
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Y
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G
G
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F
110
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R
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G
G
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F
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A
120
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K
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C
T
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Y
Y
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P
A
A
130
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L
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N
K
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M
M
F
F
C
C
Q
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L
A
A
K
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140
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T
T
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C
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P
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W
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A
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M
M
170
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T
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E
E
V
V
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V
R
R
R
R
C
C
P
P
H
H
H
H
180
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E
E
R
R
C
C
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S
D
D
S
S
D
D
G
G
L
L
A
A
190
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P
P
P
P
Q
Q
H
H
L
L
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I
R
R
V
V
E
E
G
G
200
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N
N
L
L
R
R
V
V
E
E
Y
Y
L
L
D
D
D
D
R
R
210
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N
N
T
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F
F
R
R
H
H
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V
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P
220
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Y
Y
E
E
P
P
P
P
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E
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G
G
S
S
D
D
C
C
230
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T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
N
240
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S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
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P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
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S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
N
S
S
270
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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
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R
-
K
-
K
-
G
-
E
-
P
-
H
-
H
-
E
-
L
-
300
|
P
-
P
-
G
-
S
-
T
-
K
-
R
-
A
-
L
-
P
-
310
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N
-
N
-
T
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Seliciclib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [3]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 6GGC
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.54
TM score: 0.9897
Amino acid change:
Y220C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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S
S
S
S
S
S
V
V
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P
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S
100
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Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
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S
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Y
G
G
F
F
110
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R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
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T
A
A
120
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K
K
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S
V
V
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T
C
C
T
T
Y
Y
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S
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P
A
A
130
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L
L
N
N
K
K
M
L
F
F
C
C
Q
Q
L
L
A
A
K
K
140
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T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
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T
T
P
P
P
P
P
P
G
G
T
T
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R
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V
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R
A
A
160
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M
M
A
A
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I
Y
Y
K
K
Q
Q
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S
Q
Q
H
H
M
M
170
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T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
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E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
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P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
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N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
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N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
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Y
C
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
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T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
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S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
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P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
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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
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N
N
N
N
T
T
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.Y220C (c.659A>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [3]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.Y234C (c.701A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.38  Å
PDB: 8QWO
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99189
Amino acid change:
Y234C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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S
S
S
S
S
S
V
V
P
P
S
S
100
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Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
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R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
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K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
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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
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T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
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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
C
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 Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.Y234C (c.701A>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [3]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Preclinical Drug(s)
9 drug(s) in total
Click to Show/Hide the Full List of Drugs
AMGMDS3
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R273H (c.818G>A)
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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R273H (c.818G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.V157F (c.469G>T)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.50  Å
PDB: 4KVP
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.27
TM score: 0.99738
Amino acid change:
V157F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
A
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
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
F
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
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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.V157F (c.469G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 6GGC
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.54
TM score: 0.9897
Amino acid change:
Y220C
 : 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
C
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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.Y220C (c.659A>G) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
Wild Type Structure Method: X-ray diffraction Resolution: 1.92  Å
PDB: 4QO1
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 2BIO
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.01
TM score: 0.95973
Amino acid change:
R249S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
-
L
-
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
S
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
H
-
H
-
H
-
H
-
H
-
H
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R249S (c.747G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R273C (c.817C>T)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.80  Å
PDB: 2J20
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.49
TM score: 0.99152
Amino acid change:
R273C
 : 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
C
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 HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R273C (c.817C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
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 Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R280K (c.839G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [4]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.G245S (c.733G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.15  Å
PDB: 7DHY
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.32
TM score: 0.99633
Amino acid change:
G245S
 : 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
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
S
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
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
-
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 Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.G245S (c.733G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
APR-246/Cisplatin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Ovarian cancer [ICD-11: 2C73.0] [5]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
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
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [6]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.Y163C (c.488A>G)
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
Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [6]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R273H (c.818G>A)
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
CP-31398
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Cholangiocarcinoma [ICD-11: 2C12.0] [7]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
 Disease Info 
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 6GGC
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.54
TM score: 0.9897
Amino acid change:
Y220C
 : 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
C
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 HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
Disease Class: Cholangiocarcinoma [ICD-11: 2C12.0] [7]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
 Disease Info 
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
Wild Type Structure Method: X-ray diffraction Resolution: 1.92  Å
PDB: 4QO1
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 2BIO
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.01
TM score: 0.95973
Amino acid change:
R249S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
-
L
-
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
S
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
H
-
H
-
H
-
H
-
H
-
H
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
DS-7423
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [ICD-11: 2C73.0] [8]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Resistant Drug DS-7423
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model ES-2 cells Ovary Homo sapiens (Human) CVCL_3509
TOV-21 cells Ovary Homo sapiens (Human) CVCL_3613
SKOV5 cells Ovary Homo sapiens (Human) N.A.
RMG-I cells Ascites Homo sapiens (Human) CVCL_1662
OVTOKO cells Spleen Homo sapiens (Human) CVCL_3117
OVSAHO cells Abdomen Homo sapiens (Human) CVCL_3114
OVMANA cells Ovary Homo sapiens (Human) CVCL_3111
OVKATE cells Ovary Homo sapiens (Human) CVCL_3110
OVISE cells Pelvi Homo sapiens (Human) CVCL_3116
OV1063 cells Ascites Homo sapiens (Human) CVCL_4366
SKOV5 cells Ovary Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis; Luciferase assay
Experiment for
Drug Resistance		 CCK-8 assay
HSP90 inhibitor
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug HSP90 inhibitor
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
NSC319726
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [9]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of NSC319726 by aberration of the drug's therapeutic target
Disease Class: Ovarian cancer [ICD-11: 2C73.0] [9]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of NSC319726 by aberration of the drug's therapeutic target
NSC59984
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Colorectal cancer [ICD-11: 2B91.1] [10]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Sensitive Drug NSC59984
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
RXF393 cells Kidney Homo sapiens (Human) CVCL_1673
MRC5 cells Fetal lung Homo sapiens (Human) CVCL_0440
Wi38 cells Fetal lung Homo sapiens (Human) CVCL_0579
Hop92 cells Lung Homo sapiens (Human) CVCL_1286
In Vivo Model Female CRL nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Semi-quantitative RT-PCR; Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; Colony formation assay
ReACp53
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [ICD-11: 2C73.0] [11]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.Y234C (c.701A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.38  Å
PDB: 8QWO
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99189
Amino acid change:
Y234C
 : 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
C
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 Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Head and neck cancer [ICD-11: 2D42.0] [11]
Sensitive Disease Head and neck cancer [ICD-11: 2D42.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
YW3-56
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: ER negative breast cancer [ICD-11: 2C60.7] [12]
Sensitive Disease ER negative breast cancer [ICD-11: 2C60.7]
 Disease Info 
Sensitive Drug YW3-56
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
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 Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
1833TR cells N.A. N.A. N.A.
In Vivo Model Female xenograft nude mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
EAP Protocol
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Gastric adenocarcinoma [ICD-11: 2B72.0] [13]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Sensitive Drug EAP Protocol
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.37  Å
PDB: 6VR1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.38  Å
PDB: 6VR5
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.18
TM score: 0.89418
Amino acid change:
R175H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
H
C
C
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Stomach N.A.
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway
References
Ref 1 Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.
Ref 2 Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatmentNature. 2015 Jul 16;523(7560):352-6. doi: 10.1038/nature14430. Epub 2015 May 25.
Ref 3 Roscovitine-induced apoptosis of H1299 cells depends on functional status of p53Neoplasma. 2012;59(6):606-12. doi: 10.4149/neo_2012_077.
Ref 4 Identifying the determinants of response to MDM2 inhibitionOncotarget. 2015 Apr 10;6(10):7701-12. doi: 10.18632/oncotarget.3116.
Ref 5 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.
Ref 6 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 7 CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivoTumour Biol. 2016 Jan;37(1):807-15. doi: 10.1007/s13277-015-3857-5. Epub 2015 Aug 7.
Ref 8 Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423PLoS One. 2014 Feb 4;9(2):e87220. doi: 10.1371/journal.pone.0087220. eCollection 2014.
Ref 9 Allele-specific p53 mutant reactivationCancer Cell. 2012 May 15;21(5):614-625. doi: 10.1016/j.ccr.2012.03.042.
Ref 10 Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53Cancer Res. 2015 Sep 15;75(18):3842-52. doi: 10.1158/0008-5472.CAN-13-1079. Epub 2015 Aug 20.
Ref 11 A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian CarcinomasCancer Cell. 2016 Jan 11;29(1):90-103. doi: 10.1016/j.ccell.2015.12.002. Epub 2015 Dec 31.
Ref 12 ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer CellsMol Cancer Ther. 2015 Apr;14(4):877-88. doi: 10.1158/1535-7163.MCT-14-1093-T. Epub 2015 Jan 22.
Ref 13 Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancerMol Pathol. 2003 Oct;56(5):286-92. doi: 10.1136/mp.56.5.286.

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