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

Molecular Formula	C25H27FN4O3
Molecular Weight	450.5053
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2 102 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15899831	Inhibitor 8228		1.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27025186	Primary	Phase III 663	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25895616	Primary	Phase III 663	Unknown Approved Use Unknown
Primary peritoneal cancer 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25895616	Primary	Phase III 663	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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
Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group.	2008 Apr 10	18398152
Anti-angiogenic targets in the treatment of advanced renal cell carcinoma.	2008 Dec	19075590
Novel anti-angiogenic therapies for malignant gliomas.	2008 Dec	19007739
Gateways to clinical trials. July-August 2008.	2008 Jul-Aug	18850047
Gateways to clinical trials.	2008 Oct	19088949
Targeting angiogenesis in the treatment of lung cancer.	2008 Oct	18827616
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
Novel drugs for renal cell carcinoma.	2008 Oct	18808310
[Tumor vasculature as a therapeutic target in non-small cell lung cancer].	2008 Sep	18845495
Speeding up the evaluation of new agents in cancer.	2008 Sep 3	18728279
Current available therapies and future directions in the treatment of malignant gliomas.	2009	19707392
PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment.	2009	19352490
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
VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer.	2009 Apr	19333229
An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma.	2009 Apr	19043778
Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate.	2009 Apr	18814988
Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme.	2009 Dec 16	20015387
Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors.	2009 Dec 20	19901116
Phase I study of cediranib in combination with oxaliplatin and infusional 5-Fluorouracil in patients with advanced colorectal cancer.	2009 Feb 15	19228749
Phase III trial of FOLFOX plus bevacizumab or cediranib (AZD2171) as first-line treatment of patients with metastatic colorectal cancer: HORIZON III.	2009 Jan	19203899
Antiangiogenic drugs in ovarian cancer.	2009 Jan 13	19002176
Investigational agents in the management of non-small cell lung cancer.	2009 Jul	19508832
A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients.	2009 Jul 1	19549889
VEGF inhibitors and prostate cancer therapy.	2009 Jun	19617926
Treatment in advanced colorectal cancer: what, when and how?	2009 Jun 2	19436303
Gateways to clinical trials.	2009 Mar	19455266
A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group.	2009 Mar	19091548
The vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor cediranib (Recentin; AZD2171) inhibits endothelial cell function and growth of human renal tumor xenografts.	2009 Mar 1	19215823
[Second-line treatment using novel chemotherapeutic and biologic agents].	2009 May	19461172
Current status of cediranib: the rapid development of a novel anti-angiogenic therapy.	2009 May	19450171
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
Gateways to clinical trials.	2009 Nov	20094643
Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors.	2009 Nov	19308410
Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.	2009 Nov 20	19826113
Cediranib: profile of a novel anti-angiogenic agent in patients with glioblastoma.	2009 Oct	19671039
Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function.	2009 Oct	19255759
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
VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation.	2009 Sep 18	19763275
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
Angiogenesis inhibition in prostate cancer: current uses and future promises.	2010	20169138
An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia.	2010 Feb	19674789
CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies.	2010 Jan	20009542
Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study.	2010 Jan 1	19917841
Changes in vascular permeability and expression of different angiogenic factors following anti-angiogenic treatment in rat glioma.	2010 Jan 15	20090952
Recent advances and future directions in the management of metastatic renal cell carcinoma.	2010 Mar	20184547
Tyrosine kinase inhibitors to treat liver cancer.	2010 Mar	20128706
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?	2010 Mar	20012482
Sunitinib in combination with docetaxel in patients with advanced solid tumors: a phase I dose-escalation study.	2010 Sep	20043166
Molecularly targeted therapy in hepatocellular carcinoma.	2010 Sep 1	20371362

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.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:52:58 UTC 2023` Edited by `admin` on `Wed Jul 05 23:52:58 UTC 2023`
Record UNII	NQU9IPY4K9
Record Status	`Validated (UNII)`
Record Version

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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