Drug Information

Drug (ID: DG01502) and It's Reported Resistant Information
Name
Cediranib
Synonyms
Cediranib; 288383-20-0; Recentin; AZD2171; Cedirannib; Cediranib (AZD2171); AZD 2171; AZD-2171; 4-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; Cediranib free base; 4-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline; Cediranib (AZD217); UNII-NQU9IPY4K9; NQU9IPY4K9; ZD-2171; AZD-2171 maleate; 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline; 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline; CHEMBL491473; 288383-20-0 (free base); NSC-732208; 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; C25H27FN4O3; Cediranib (USAN/INN); Cediranib [USAN:INN:BAN]; 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; Cediranib,AZD2171; Kinome_3318; Cediranib dihydrochloride; AZD2171, Cediranib; Cediranib - AZD2171; SCHEMBL63147; MLS006010063; GTPL5664; QCR-93; CHEBI:94782; AOB1949; DTXSID10183035; BCPP000295; HMS3654G05; HMS3674G17; HMS3744O21; AMY16021; BCP01378; EX-A2039; ZINC3948085; BDBM50331096; MFCD09954115; NSC755606; NSC800069; s1017; AKOS005145767; BCP9000500; CCG-264679; CS-0119; DB04849; ES-0052; NSC-755606; NSC-800069; SB16536; ZD 2171; NCGC00263097-01; NCGC00263097-09; AC-25033; HY-10205; Quinazoline,4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]-; SMR004701223; FT-0751000; SW219261-1; X2636; EC-000.2328; A24280; D08881; Q-101399; Q5057052; BRD-K86930074-001-01-9; 4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-yl-propoxy)-quinazoline; AV3; Quinazoline, 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(1-pyrrolidinyl)propoxy)-
    Click to Show/Hide
Indication
In total 2 Indication(s)
Ovarian cancer [ICD-11: 2C73]
Phase 3
[1]
Ovarian cancer [ICD-11: 2C73]
Phase 3
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Bladder cancer [ICD-11: 2C94]
[1]
Target Poly [ADP-ribose] polymerase (PARP) NOUNIPROTAC [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
8
IsoSMILES
CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NC4=CC(=C(C=C43)OC)OCCCN5CCCC5
InChI
InChI=1S/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3
InChIKey
XXJWYDDUDKYVKI-UHFFFAOYSA-N
PubChem CID
9933475
ChEBI ID
CHEBI:94782
TTD Drug ID
D01SHZ
VARIDT ID
DR1886
DrugBank ID
DB04849
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 Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K660E (c.1978A>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K660N (c.1980G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.W290C (c.870G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target
Endometrial cancer [ICD-11: 2C76]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Bladder cancer [ICD-11: 2C94]
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: Fibroblast growth factor receptor 3 (FGFR3) [1]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y375C (c.1124A>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.Y375C (c.1124A>G) in gene FGFR3 cause the resistance of Cediranib by unusual activation of pro-survival pathway
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S249C (c.746C>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
References
Ref 1 Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
Ref 2 Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinomaCancer Res. 2013 Aug 15;73(16):5195-205. doi: 10.1158/0008-5472.CAN-12-3950. Epub 2013 Jun 20.

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