Drug Information

Drug (ID: DG01627) and It's Reported Resistant Information
Name
TAS-121
Synonyms
UNII-Z36593C4RW; Z36593C4RW; SCHEMBL15220964; TAS-121; (S)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)acrylamide; 1451370-01-6; 2-Propenamide, N-((8S)-4-amino-6,7,8,9-tetrahydro-5-(3-quinolinyl)pyrimido(5,4-b)indolizin-8-yl)-; N-((8S)-4-Amino-6,7,8,9-tetrahydro-5-(3-quinolinyl)pyrimido(5,4-b)indolizin-8-yl)-2-propenamide
    Click to Show/Hide
Structure
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
3
IsoSMILES
C=CC(=O)N[C@H]1CCC2=C(C3=C(N=CN=C3N2C1)N)C4=CC5=CC=CC=C5N=C4
InChI
InChI=1S/C22H20N6O/c1-2-18(29)27-15-7-8-17-19(14-9-13-5-3-4-6-16(13)24-10-14)20-21(23)25-12-26-22(20)28(17)11-15/h2-6,9-10,12,15H,1,7-8,11H2,(H,27,29)(H2,23,25,26)/t15-/m0/s1
InChIKey
POOPTPRMXSYFRV-HNNXBMFYSA-N
PubChem CID
71682991
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
Colorectal cancer [ICD-11: 2B91]
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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) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G719S (c.2155G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC827 cells Lung Homo sapiens (Human) CVCL_2063
HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
SW48 cells Colon Homo sapiens (Human) CVCL_1724
NCI-H1975 cells Lung Homo sapiens (Human) CVCL_1511
In Vivo Model Male BALB/cA nude mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 CellTiter-Glo assay; IC50 assay
Lung cancer [ICD-11: 2C25]
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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) [1]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 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
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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 Revealed Based on the Cell Line Data
In Vitro Model HCC827 cells Lung Homo sapiens (Human) CVCL_2063
HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
SW48 cells Colon Homo sapiens (Human) CVCL_1724
NCI-H1975 cells Lung Homo sapiens (Human) CVCL_1511
In Vivo Model Male BALB/cA nude mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 CellTiter-Glo assay; IC50 assay
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G719S (c.2155G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC827 cells Lung Homo sapiens (Human) CVCL_2063
HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
SW48 cells Colon Homo sapiens (Human) CVCL_1724
NCI-H1975 cells Lung Homo sapiens (Human) CVCL_1511
In Vivo Model Male BALB/cA nude mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 CellTiter-Glo assay; IC50 assay
References
Ref 1 TAS-121, A Selective Mutant EGFR Inhibitor, Shows Activity Against Tumors Expressing Various EGFR Mutations Including T790M and Uncommon Mutations G719XMol Cancer Ther. 2019 May;18(5):920-928. doi: 10.1158/1535-7163.MCT-18-0645. Epub 2019 Mar 14.

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