Drug Information

Drug (ID: DG01675) and It's Reported Resistant Information
Name
AMGMDS3
Synonyms
AMGMDS3; Q59770979
    Click to Show/Hide
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
9
IsoSMILES
CC[C@@H](C(=O)OCC)N1[C@@H]([C@H]([C@](CC1=O)(C)CC(=O)O)C2=CC(=CC=C2)Cl)C3=CC(=CC=C3)Cl
InChI
InChI=1S/C26H29Cl2NO5/c1-4-20(25(33)34-5-2)29-21(30)14-26(3,15-22(31)32)23(16-8-6-10-18(27)12-16)24(29)17-9-7-11-19(28)13-17/h6-13,20,23-24H,4-5,14-15H2,1-3H3,(H,31,32)/t20-,23+,24+,26-/m0/s1
InChIKey
SZACTBIUKXKQGM-YLJDOISLSA-N
PubChem CID
139033635
Type(s) of Resistant Mechanism of This Drug
  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
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 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 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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V157F (c.469G>T)
 Molecule Info 
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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
 Molecule Info 
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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R273C (c.817C>T)
 Molecule Info 
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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
 Molecule Info 
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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 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 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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.G245S (c.733G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.15  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
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R158H (c.473G>A)
 Molecule Info 
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.R158H (c.473G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R158L (c.473G>T)
 Molecule Info 
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.R158L (c.473G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R248W (c.742C>T)
 Molecule Info 
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.R248W (c.742C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
 Molecule Info 
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.R248Q (c.743G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R280T (c.839G>C)
 Molecule Info 
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.R280T (c.839G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
References
Ref 1 Identifying the determinants of response to MDM2 inhibitionOncotarget. 2015 Apr 10;6(10):7701-12. doi: 10.18632/oncotarget.3116.

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