Drug Information

Drug (ID: DG01896) and It's Reported Resistant Information
Name
EKI-285
Synonyms
EKI-285
    Click to Show/Hide
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[1]
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
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 Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L858R (c.2573T>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.64  Å
PDB: 4LI5
Mutant Type Structure Method: X-ray diffraction Resolution: 2.47  Å
PDB: 2ITV
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.90001
Amino acid change:
L858R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
M
-
G
G
E
E
A
A
P
P
700
|
N
N
Q
Q
A
A
L
L
L
L
R
R
I
I
L
L
K
K
E
E
710
|
T
T
E
E
F
F
K
K
K
K
I
I
K
K
V
V
L
L
G
G
720
|
S
S
G
G
A
A
F
F
G
G
T
T
V
V
Y
Y
K
K
G
G
730
|
L
L
W
W
I
I
P
P
E
E
G
G
E
E
K
K
V
V
K
K
740
|
I
I
P
P
V
V
A
A
I
I
K
K
E
E
L
L
R
R
E
E
750
|
A
A
T
T
S
S
P
P
K
K
A
A
N
N
K
K
E
E
I
I
760
|
L
L
D
D
E
E
A
A
Y
Y
V
V
M
M
A
A
S
S
V
V
770
|
D
D
N
N
P
P
H
H
V
V
C
C
R
R
L
L
L
L
G
G
780
|
I
I
C
C
L
L
T
T
S
S
T
T
V
V
Q
Q
L
L
I
I
790
|
T
T
Q
Q
L
L
M
M
P
P
F
F
G
G
C
C
L
L
L
L
800
|
D
D
Y
Y
V
V
R
R
E
E
H
H
K
K
D
D
N
N
I
I
810
|
G
G
S
S
Q
Q
Y
Y
L
L
L
L
N
N
W
W
C
C
V
V
820
|
Q
Q
I
I
A
A
K
K
G
G
M
M
N
N
Y
Y
L
L
E
E
830
|
D
D
R
R
R
R
L
L
V
V
H
H
R
R
D
D
L
L
A
A
840
|
A
A
R
R
N
N
V
V
L
L
V
V
K
K
T
T
P
P
Q
Q
850
|
H
H
V
V
K
K
I
I
T
T
D
D
F
F
G
G
L
R
A
A
860
|
K
K
L
L
L
L
G
G
A
A
E
E
E
E
K
K
E
E
Y
Y
870
|
H
H
A
A
E
E
G
G
G
G
K
K
V
V
P
P
I
I
K
K
880
|
W
W
M
M
A
A
L
L
E
E
S
S
I
I
L
L
H
H
R
R
890
|
I
I
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
900
|
Y
Y
G
G
V
V
T
T
V
V
W
W
E
E
L
L
M
M
T
T
910
|
F
F
G
G
S
S
K
K
P
P
Y
Y
D
D
G
G
I
I
P
P
920
|
A
A
S
S
E
E
I
I
S
S
S
S
I
I
L
L
E
E
K
K
930
|
G
G
E
E
R
R
L
L
P
P
Q
Q
P
P
P
P
I
I
C
C
940
|
T
T
I
I
D
D
V
V
Y
Y
M
M
I
I
M
M
V
V
K
K
950
|
C
C
W
W
M
M
I
I
D
D
A
A
D
D
S
S
R
R
P
P
960
|
K
K
F
F
R
R
E
E
L
L
I
I
I
I
E
E
F
F
S
S
970
|
K
K
M
M
A
A
R
R
D
D
P
P
Q
Q
R
R
Y
Y
L
L
980
|
V
V
I
I
Q
Q
G
G
D
D
E
E
R
R
M
M
H
H
L
L
990
|
P
P
S
S
P
P
T
T
D
D
S
S
N
N
F
F
Y
Y
R
R
1000
|
A
A
L
L
M
M
D
D
E
E
E
E
D
D
M
M
D
D
D
D
1010
|
V
V
V
V
D
D
A
A
D
D
E
E
Y
Y
L
L
I
I
P
P
1020
|
Q
Q
-
Q
-
G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung adenocarcinomas tissue N.A.
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Key Molecule: Epidermal growth factor receptor (EGFR) [3]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L844V (c.2530C>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC827 cells Lung Homo sapiens (Human) CVCL_2063
PC9 cells Lung Homo sapiens (Human) CVCL_B260
H3255 cells Lung Homo sapiens (Human) CVCL_6831
HCC827EP cells Lung Homo sapiens (Human) CVCL_2063
H3255DR cells Lung Homo sapiens (Human) CVCL_DI56
H197 cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; CytoSelect 96-well cell transformation assay
Key Molecule: Epidermal growth factor receptor (EGFR) [3]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L718Q (c.2153T>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC827 cells Lung Homo sapiens (Human) CVCL_2063
PC9 cells Lung Homo sapiens (Human) CVCL_B260
H3255 cells Lung Homo sapiens (Human) CVCL_6831
HCC827EP cells Lung Homo sapiens (Human) CVCL_2063
H3255DR cells Lung Homo sapiens (Human) CVCL_DI56
H197 cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; CytoSelect 96-well cell transformation assay
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H773L (c.2318A>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH-H1975 N.A. N.A. N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.H773L (c.2318A>T) in gene EGFR cause the resistance of EKI-285 by aberration of the drug's therapeutic target
References
Ref 1 Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-mutant lung cancer reveals novel treatment strategiesCancer Res. 2007 Nov 1;67(21):10417-27. doi: 10.1158/0008-5472.CAN-07-1248.
Ref 2 Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006 Nov 1;12(21):6494-501. doi: 10.1158/1078-0432.CCR-06-1570.
Ref 3 EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR InhibitorsClin Cancer Res. 2015 Sep 1;21(17):3913-23. doi: 10.1158/1078-0432.CCR-14-2789. Epub 2015 May 6.
Ref 4 Differential sensitivity of ERBB2 kinase domain mutations towards lapatinibPLoS One. 2011;6(10):e26760. doi: 10.1371/journal.pone.0026760. Epub 2011 Oct 28.

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