Drug Information

Drug (ID: DG00213) and It's Reported Resistant Information
Name
Savolitinib
Synonyms
1313725-88-0; AZD-6094; AZD6094; UNII-2A2DA6857R; CHEMBL3334567; 2A2DA6857R; Savolitinib [INN]; Volitinib(Savolitinib); Savolitinib [USAN:INN]; GTPL9918; SCHEMBL12489208; EX-A845; BDBM50023342; ZINC149738712; AKOS030526403; DB12048; compound 28 [PMID: 25148209]; HY-15959; AS-35250; 1H-1,2,3-Triazolo(4,5-b)pyrazine, 1-((1S)-1-imidazo(1,2-a)pyridin-6-ylethyl)-6-(1-methyl-1H-pyrazol-4-yl)-; KB-333895; FT-0700162; J-690125; 4-{1-[(1S)-1-{imidazo[1,2-a]pyri
    Click to Show/Hide
Indication
In total 2 Indication(s)
Renal cell carcinoma [ICD-11: 2C90]
Phase 3
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[1]
Target Proto-oncogene c-Met (MET) MET_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C17H15N9
IsoSMILES
C[C@@H](C1=CN2C=CN=C2C=C1)N3C4=NC(=CN=C4N=N3)C5=CN(N=C5)C
InChI
1S/C17H15N9/c1-11(12-3-4-15-18-5-6-25(15)10-12)26-17-16(22-23-26)19-8-14(21-17)13-7-20-24(2)9-13/h3-11H,1-2H3/t11-/m0/s1
InChIKey
XYDNMOZJKOGZLS-NSHDSACASA-N
PubChem CID
68289010
TTD Drug ID
D0LW0T
DrugBank ID
DB12048
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
Lung cancer [ICD-11: 2C25]
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: Hepatocyte growth factor receptor (MET) [1]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D1228V
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 5HNI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.67  Å
PDB: 6SDC
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.85
TM score: 0.88477
Amino acid change:
D1228V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
G
-
D
1040
|
-
S
-
D
-
I
-
S
-
S
-
P
-
L
-
L
-
Q
N
N
1050
|
T
T
V
V
H
H
I
I
D
D
L
L
S
S
A
A
L
L
N
N
1060
|
P
P
E
E
L
L
V
V
Q
Q
A
A
V
V
Q
Q
H
H
V
V
1070
|
V
V
I
I
G
G
P
P
S
S
S
S
L
L
I
I
V
V
H
H
1080
|
F
F
N
N
E
E
V
V
I
I
G
G
R
R
G
G
H
H
F
F
1090
|
G
G
C
C
V
V
Y
Y
H
H
G
G
T
T
L
L
L
L
D
D
1100
|
N
N
D
D
G
G
K
K
K
K
I
I
H
H
C
C
A
A
V
V
1110
|
K
K
S
S
L
L
N
N
R
R
I
I
T
T
D
D
I
I
G
G
1120
|
E
E
V
V
S
S
Q
Q
F
F
L
L
T
T
E
E
G
G
I
I
1130
|
I
I
M
M
K
K
D
D
F
F
S
S
H
H
P
P
N
N
V
V
1140
|
L
L
S
S
L
L
L
L
G
G
I
I
C
C
L
L
R
R
S
S
1150
|
E
E
G
G
S
S
P
P
L
L
V
V
V
V
L
L
P
P
Y
Y
1160
|
M
M
K
K
H
H
G
G
D
D
L
L
R
R
N
N
F
F
I
I
1170
|
R
R
N
N
E
E
T
T
H
H
N
N
P
P
T
T
V
V
K
K
1180
|
D
D
L
L
I
I
G
G
F
F
G
G
L
L
Q
Q
V
V
A
A
1190
|
K
K
G
G
M
M
K
K
F
Y
L
L
A
A
S
S
K
K
K
K
1200
|
F
F
V
V
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
1210
|
C
C
M
M
L
L
D
D
E
E
K
K
F
F
T
T
V
V
K
K
1220
|
V
V
A
A
D
D
F
F
G
G
L
L
A
A
R
R
D
V
M
M
1230
|
Y
Y
D
D
K
K
E
E
F
Y
D
Y
S
S
V
V
H
H
N
N
1240
|
K
K
T
T
G
G
A
A
K
K
L
L
P
P
V
V
K
K
W
W
1250
|
M
M
A
A
L
L
E
E
S
S
L
L
Q
Q
T
T
Q
Q
K
K
1260
|
F
F
T
T
T
T
K
K
S
S
D
D
V
V
W
W
S
S
F
F
1270
|
G
G
V
V
L
L
L
L
W
W
E
E
L
L
M
M
T
T
R
R
1280
|
G
G
A
A
P
P
P
P
Y
Y
P
P
D
D
V
V
N
N
T
T
1290
|
F
F
D
D
I
I
T
T
V
V
Y
Y
L
L
L
L
Q
Q
G
G
1300
|
R
R
R
R
L
L
L
L
Q
Q
P
P
E
E
Y
Y
C
C
P
P
1310
|
D
D
P
P
L
L
Y
Y
E
E
V
V
M
M
L
L
K
K
C
C
1320
|
W
W
H
H
P
P
K
K
A
A
E
E
M
M
R
R
P
P
S
S
1330
|
F
F
S
S
E
E
L
L
V
V
S
S
R
R
I
I
S
S
A
A
1340
|
I
I
F
F
S
S
T
T
F
F
I
I
G
G
E
-
H
-
Y
-
1350
|
V
-
H
-
V
-
N
-
A
-
T
-
Y
-
V
-
N
-
V
-
1360
|
K
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model PC9 cells Lung Homo sapiens (Human) CVCL_B260
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 MTS assay
Mechanism Description Our in vitro findings demonstrate that MET D1228V induces resistance to type I MET TkIs through impaired drug binding while sensitivity to type II MET TkIs is maintained.
References
Ref 1 Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer. Cancer Discov. 2016 Dec;6(12):1334-1341. doi: 10.1158/2159-8290.CD-16-0686. Epub 2016 Sep 30.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.