CEDIRANIB

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

Structure Search

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
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2016/10/WC500214183.pdf | https://www.ncbi.nlm.nih.gov/pubmed/15899831

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 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15899831	Inhibitor 8297		1.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27025186	Primary	Phase III 656	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25895616	Primary	Phase III 656	Unknown Approved Use Unknown
Primary peritoneal cancer 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25895616	Primary	Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Targeted Therapies in Cancer - Fourth International Congress. Angiogenesis inhibition.	2005 Dec	16320129
Angiogenesis and lung cancer: prognostic and therapeutic implications.	2005 May 10	15886312
Defective differentiation of myeloid and plasmacytoid dendritic cells in advanced cancer patients is not normalized by tyrosine kinase inhibition of the vascular endothelial growth factor receptor.	2007	18320010
Tracking normalization of brain tumor vasculature by magnetic imaging and proangiogenic biomarkers.	2007 Jan	17222788
Vascular endothelial growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: a review of recent clinical trials.	2007 May	18473996
Gateways to clinical trials. July-August 2008.	2008 Jul-Aug	18850047
The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies.	2008 Jun	18520296
The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis.	2008 Jun 15	18559522
Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy.	2008 May 15	18483380
Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts.	2008 Oct	18819995
Acoustic radiation force and optical spectroscopy for assessing tumor vessel normalization during anti-angiogenic therapy.	2009	19964240
Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model.	2009	19277878
Antitumor and antiangiogenic activity of cediranib in a preclinical model of renal cell carcinoma.	2009 Dec	20044618
Antiangiogenic drugs in ovarian cancer.	2009 Jan 13	19002176
Investigational agents in the management of non-small cell lung cancer.	2009 Jul	19508832
Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice.	2009 May 20	19332720
Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines.	2009 Sep	19755510
DCE-MRI assessment of the effect of vandetanib on tumor vasculature in patients with advanced colorectal cancer and liver metastases: a randomized phase I study.	2009 Sep 21	19946413
Targeted therapies in epithelial ovarian cancer.	2010	20111741
Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor inhibitor.	2010 Mar	20056761
Sunitinib in combination with docetaxel in patients with advanced solid tumors: a phase I dose-escalation study.	2010 Sep	20043166

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.

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

Quinazoline, 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]-

Systematic Name

English

4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-6-METHOXY-7-(3-PYRROLIDIN-1-YLPROPOXY)QUINAZOLINE

Systematic Name

English

CEDIRANIB [MART.]

Common Name

English

AZD2171

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1967