CEDIRANIB

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H27FN4O3
Molecular Weight	450.5053
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=C(OCCCN2CCCC2)C=C3N=CN=C(OC4=C(F)C5=C(NC(C)=C5)C=C4)C3=C1

InChI

InChIKey=XXJWYDDUDKYVKI-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description

Cediranib (AZD-2171) is a VEGFR-2 kinase inhibitor which was developed by AstraZeneca for the treatment of cancer. The drug reached the final stage of approval by European Medicines Agency in 2008 under the name Zemfirza (it was recommended to be taken in combination with platinum-based chemotherapy), however on 19 September 2016 AstraZeneca decided to withdraw the Marketing Authorisation Application.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vascular endothelial growth factor receptor 2	Inhibitor		1.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer	Primary	Phase III	Unknown
Fallopian tube cancer	Primary	Phase III	Unknown
Primary peritoneal cancer	Primary	Phase III	Unknown

C_max

Value	Dose	Analyte	Population
1.02 ng/mL	0.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
1.9 ng/mL	1 mg single, oral	CEDIRANIB plasma	Homo sapiens
5.1 ng/mL	2.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
7.02 ng/mL	5 mg single, oral	CEDIRANIB plasma	Homo sapiens
24.8 ng/mL	10 mg single, oral	CEDIRANIB plasma	Homo sapiens
45.7 ng/mL	20 mg single, oral	CEDIRANIB plasma	Homo sapiens
73.1 ng/mL	30 mg single, oral	CEDIRANIB plasma	Homo sapiens
96.9 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
217 ng/mL	60 mg single, oral	CEDIRANIB plasma	Homo sapiens
1.39 ng/mL	0.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1.79 ng/mL	1 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
9.37 ng/mL	2.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
13.4 ng/mL	5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
42.8 ng/mL	10 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
66.6 ng/mL	20 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
69.6 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
73.9 ng/mL	45 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
170 ng/mL	60 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1.36 ng/mL	1 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
3.02 ng/mL	2.5 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
6.78 ng/mL	5 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
25.8 ng/mL	10 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
25.7 ng/mL	20 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
52.6 ng/mL	30 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
2.33 ng/mL	1 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
5.28 ng/mL	2.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
17.3 ng/mL	5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
18.8 ng/mL	10 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
40.4 ng/mL	20 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
118 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
113 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
115 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
138 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
47 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
96 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
64.2 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
88.9 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
72 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
42.2 ng/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
87.3 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
127.9 ng/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
15.6 ng × h/mL	0.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
32.3 ng × h/mL	1 mg single, oral	CEDIRANIB plasma	Homo sapiens
87.1 ng × h/mL	2.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
117 ng × h/mL	5 mg single, oral	CEDIRANIB plasma	Homo sapiens
457 ng × h/mL	10 mg single, oral	CEDIRANIB plasma	Homo sapiens
865 ng × h/mL	20 mg single, oral	CEDIRANIB plasma	Homo sapiens
1190 ng × h/mL	30 mg single, oral	CEDIRANIB plasma	Homo sapiens
2190 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
3590 ng × h/mL	60 mg single, oral	CEDIRANIB plasma	Homo sapiens
17.3 ng × h/mL	0.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
24.3 ng × h/mL	1 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
102 ng × h/mL	2.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
196 ng × h/mL	5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
502 ng × h/mL	10 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
774 ng × h/mL	20 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
741 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1060 ng × h/mL	45 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1860 ng × h/mL	60 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
15.5 ng × h/mL	1 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
34.9 ng × h/mL	2.5 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
97.4 ng × h/mL	5 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
302 ng × h/mL	10 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
309 ng × h/mL	20 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
565 ng × h/mL	30 mg 1 times / day multiple, oral	CEDIRANIB plasma	Homo sapiens
25.1 ng × h/mL	1 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
95.3 ng × h/mL	2.5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
226 ng × h/mL	5 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
316 ng × h/mL	10 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
559 ng × h/mL	20 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
2005 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
2238 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
1857 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
3427 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
1248 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
1213 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
877 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1106 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
958.1 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
805 ng × h/mL	30 mg 1 times / day steady-state, oral	CEDIRANIB plasma	Homo sapiens
1920 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
2392 ng × h/mL	45 mg single, oral	CEDIRANIB plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
16.6 h	0.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
22.2 h	1 mg single, oral	CEDIRANIB plasma	Homo sapiens
16.5 h	2.5 mg single, oral	CEDIRANIB plasma	Homo sapiens
25.6 h	5 mg single, oral	CEDIRANIB plasma	Homo sapiens
18.8 h	10 mg single, oral	CEDIRANIB plasma	Homo sapiens
21.7 h	20 mg single, oral	CEDIRANIB plasma	Homo sapiens
19.7 h	30 mg single, oral	CEDIRANIB plasma	Homo sapiens
25.7 h	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
27.2 h	60 mg single, oral	CEDIRANIB plasma	Homo sapiens
19.7 h	45 mg single, oral	CEDIRANIB plasma	Homo sapiens
25.6 h	45 mg single, oral	CEDIRANIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
4.6%			CEDIRANIB plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
45 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT	DLT: Proteinuria, Diarrhea...
30 mg 1 times / day multiple, oral MTD	unhealthy, ADULT
12 mg/m2 1 times / day multiple, oral MTD	unhealthy, CHILD\|ADOLESCENT	DLT: Diarrhea...
12 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, CHILD\|ADOLESCENT	DLT: Lethargy, Nausea...
17 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, CHILD\|ADOLESCENT	DLT: Nausea, anorexi...

Showing 1 to 5 of 5 entries

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AEs

Show entries

AE	Significance	Dose	Population
Diarrhea	16.7% DLT	45 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Thrombocytopenia	16.7% DLT	45 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Proteinuria	33.3% DLT	45 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Diarrhea	grade 3, 16.7% DLT	12 mg/m2 1 times / day multiple, oral MTD	unhealthy, CHILD\|ADOLESCENT
Nausea	grade 3, 50% DLT	12 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, CHILD\|ADOLESCENT

Showing 1 to 5 of 11 entries

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PubMed

Show entries

Title	Date	PubMed
Gateways to clinical trials.	2006 Dec	17235418
Vascular endothelial growth factor tyrosine kinase inhibitor AZD2171 and fractionated radiotherapy in mouse models of lung cancer.	2006 Dec 1	17145887
Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit.	2007 Feb	17308057
AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients.	2007 Jan	17222792
Gateways to clinical trials.	2007 Jul-Aug	17922073

Showing 1 to 5 of 19 entries

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 20 mg taken orally, once daily.

Route of Administration: Oral

In Vitro Use Guide

NCI-H526 cells were treated with Cediranib for 72 hours (0.001 nM, 0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM). Cediranib inhibited SCF-stimulated proliferation of cells with an IC50 value of 0.013 nmol/L.

Show entries

Name

Type

Language

CEDIRANIB

Official Name

English

CEDIRANIB [USAN]

Common Name

English

AZD-2171

Code

English

cediranib [INN]

Common Name

English

Cediranib [WHO-DD]

Common Name

English

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Classification Tree

Code System

Code

Protein Kinase Inhibitor

NCI_THESAURUS

C1967

Antineoplastic Agent

NCI_THESAURUS

C1742

Designated

FDA ORPHAN DRUG

310510

Protein kinase inhibitors

WHO-ATC

L01XE32

Positive

EU-Orphan Drug

EU/3/14/1303

Showing 1 to 5 of 5 entries

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Code System

Code

Type

Description

CAS

288383-20-0

PRIMARY

INN

8764

PRIMARY

USAN

TT-141

PRIMARY

NCI_THESAURUS

C80867

PRIMARY

EPA CompTox

DTXSID10183035

PRIMARY

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ACTIVE MOIETY


					NQU9IPY4K9

CEDIRANIB

METABOLITE (PARENT)


					X2QY7DFS1F

QUINAZOLINE, 4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-6-METHOXY-7-(3-(1-OXIDO-1-PYRROLIDINYL)PROPOXY)-

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound