Drug Information

Drug (ID: DG00471) and It's Reported Resistant Information
Name
Exemestane/Everolimus
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Breast cancer [ICD-11: 2C60]
[1]
COVID-19 [ICD-11: 1D92]
[2]
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
Breast cancer [ICD-11: 2C60]
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: Estrogen receptor alpha (ESR1) [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.Y537S
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 2IOG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.50  Å
PDB: 5DXE
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.7
TM score: 0.91757
Amino acid change:
Y537S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
D
-
P
-
M
-
I
-
K
300
|
-
R
-
S
-
K
-
K
-
N
-
S
-
L
-
A
-
L
S
S
310
|
L
L
T
T
A
A
D
D
Q
Q
M
M
V
V
S
S
A
A
L
L
320
|
L
L
D
D
A
A
E
E
P
P
P
P
I
I
L
L
Y
Y
S
S
330
|
E
E
Y
Y
D
D
P
P
T
T
R
R
P
P
F
F
S
S
E
E
340
|
A
A
S
S
M
M
M
M
G
G
L
L
L
L
T
T
N
N
L
L
350
|
A
A
D
D
R
R
E
E
L
L
V
V
H
H
M
M
I
I
N
N
360
|
W
W
A
A
K
K
R
R
V
V
P
P
G
G
F
F
V
V
D
D
370
|
L
L
T
T
L
L
H
H
D
D
Q
Q
V
V
H
H
L
L
L
L
380
|
E
E
C
-
A
A
W
W
L
L
E
E
I
I
L
L
M
M
I
I
390
|
G
G
L
L
V
V
W
W
R
R
S
S
M
M
E
E
H
H
P
P
400
|
G
G
K
K
L
L
L
L
F
F
A
A
P
P
N
N
L
L
L
L
410
|
L
L
D
D
R
R
N
N
Q
Q
G
G
K
K
C
-
V
V
E
E
420
|
G
G
M
M
V
V
E
E
I
I
F
F
D
D
M
M
L
L
L
L
430
|
A
A
T
T
S
S
S
S
R
R
F
F
R
R
M
M
M
M
N
N
440
|
L
L
Q
Q
G
G
E
E
E
E
F
F
V
V
C
C
L
L
K
K
450
|
S
S
I
I
I
I
L
L
L
L
N
N
S
S
G
G
V
V
Y
Y
460
|
T
T
F
F
L
L
S
S
S
S
T
T
L
L
K
K
S
S
L
L
470
|
E
E
E
E
K
K
D
D
H
H
I
I
H
H
R
R
V
V
L
L
480
|
D
D
K
K
I
I
T
T
D
D
T
T
L
L
I
I
H
H
L
L
490
|
M
M
A
A
K
K
A
A
G
G
L
L
T
T
L
L
Q
Q
Q
Q
500
|
Q
Q
H
H
Q
Q
R
R
L
L
A
A
Q
Q
L
L
L
L
L
L
510
|
I
I
L
L
S
S
H
H
I
I
R
R
H
H
M
M
S
S
N
N
520
|
K
K
G
G
M
M
E
E
H
H
L
L
Y
Y
S
S
M
M
K
K
530
|
C
-
K
K
N
N
V
V
V
V
P
P
L
L
Y
S
D
D
L
L
540
|
L
L
L
L
E
E
M
M
L
L
D
D
A
A
H
H
R
R
L
L
550
|
H
H
A
A
P
P
T
T
S
S
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Overall survival assay
Mechanism Description All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.
Key Molecule: Estrogen receptor alpha (ESR1) [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.D538G
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 2IOG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 4PXM
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.86
TM score: 0.90649
Amino acid change:
D538G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
V
-
D
-
L
-
G
-
T
-
E
290
|
-
N
-
L
-
Y
-
F
-
Q
-
S
-
N
-
A
-
M
-
K
300
|
-
R
-
S
-
K
-
K
-
N
-
S
-
L
-
A
-
L
S
S
310
|
L
L
T
T
A
A
D
D
Q
Q
M
M
V
V
S
S
A
A
L
L
320
|
L
L
D
D
A
A
E
E
P
P
P
P
I
I
L
L
Y
Y
S
S
330
|
E
E
Y
Y
D
D
P
P
T
T
R
R
P
P
F
F
S
S
E
E
340
|
A
A
S
S
M
M
M
M
G
G
L
L
L
L
T
T
N
N
L
L
350
|
A
A
D
D
R
R
E
E
L
L
V
V
H
H
M
M
I
I
N
N
360
|
W
W
A
A
K
K
R
R
V
V
P
P
G
G
F
F
V
V
D
D
370
|
L
L
T
T
L
L
H
H
D
D
Q
Q
V
V
H
H
L
L
L
L
380
|
E
E
C
C
A
A
W
W
L
L
E
E
I
I
L
L
M
M
I
I
390
|
G
G
L
L
V
V
W
W
R
R
S
S
M
M
E
E
H
H
P
P
400
|
G
G
K
K
L
L
L
L
F
F
A
A
P
P
N
N
L
L
L
L
410
|
L
L
D
D
R
R
N
N
Q
Q
G
G
K
K
C
C
V
V
E
E
420
|
G
G
M
M
V
V
E
E
I
I
F
F
D
D
M
M
L
L
L
L
430
|
A
A
T
T
S
S
S
S
R
R
F
F
R
R
M
M
M
M
N
N
440
|
L
L
Q
Q
G
G
E
E
E
E
F
F
V
V
C
C
L
L
K
K
450
|
S
S
I
I
I
I
L
L
L
L
N
N
S
S
G
G
V
V
Y
Y
460
|
T
T
F
F
L
L
S
S
S
S
T
T
L
L
K
K
S
S
L
L
470
|
E
E
E
E
K
K
D
D
H
H
I
I
H
H
R
R
V
V
L
L
480
|
D
D
K
K
I
I
T
T
D
D
T
T
L
L
I
I
H
H
L
L
490
|
M
M
A
A
K
K
A
A
G
G
L
L
T
T
L
L
Q
Q
Q
Q
500
|
Q
Q
H
H
Q
Q
R
R
L
L
A
A
Q
Q
L
L
L
L
L
L
510
|
I
I
L
L
S
S
H
H
I
I
R
R
H
H
M
M
S
S
N
N
520
|
K
K
G
G
M
M
E
E
H
H
L
L
Y
Y
S
S
M
M
K
K
530
|
C
C
K
K
N
N
V
V
V
V
P
P
L
L
Y
Y
D
G
L
L
540
|
L
L
L
L
E
E
M
M
L
L
D
D
A
A
H
H
R
R
L
L
550
|
H
H
A
A
P
P
T
T
S
S
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Overall survival assay
Mechanism Description All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.
Key Molecule: Estrogen receptor alpha (ESR1) [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.L536_D538>P
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Overall survival assay
Mechanism Description All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.
References
Ref 1 Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015 Nov 11;8:3323-8. doi: 10.2147/OTT.S92443. eCollection 2015.
Ref 2 Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies Nat Med. 2021 Apr;27(4):717-726. doi: 10.1038/s41591-021-01294-w. Epub 2021 Mar 4.

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