Cediranib

Identification

Name
Cediranib
Accession Number
DB04849
Description

The novel indole-ether quinazoline Cediranib is a highly potent (IC50 < 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro. It is being developed clinically as a once-daily oral therapy for the treatment of cancer.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 450.5053
Monoisotopic: 450.206718955
Chemical Formula
C25H27FN4O3
Synonyms
Not Available
External IDs
  • AZD-2171
  • AZD2171

Pharmacology

Indication

For the treatment of liver cancer, advanced non-small cell lung cancer (NSCLC), advanced colorectal cancer (CRC) and other solid tumors.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Cediranib is a once-daily, orally available, highly potent and selective VEGF signalling inhibitor that inhibits all three VEGF receptors. The preclinical profile of Cediranib indicates that it has the potential to be the 'best in class' VEGF signalling inhibitor. Phase I data indicate that Cediranib is generally well tolerated, with the most common dose related adverse events being diarrhoea, hoarseness, headache and hypertension.

Mechanism of action

Cediranib inhibits vacular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK). By forming a blockade at the VEGF receptors, Cediranib limits the growth of new blood vessels, which are essential to supporting tumor growth. Thus, lacking sufficient blood supply, tumor cells become starved for nutrients, slowing or halting growth and potentially improving the efficacy of other treatments. Preclinical evidence indicated that the drug had a high affinity at these sites, and was well tolerated and efficacious in animal studies.

TargetActionsOrganism
UVascular endothelial growth factor receptor 2Not AvailableHumans
Absorption

Available following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

12 to 35 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Cediranib.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Cediranib.
CarbimazoleThe therapeutic efficacy of Carbimazole can be decreased when used in combination with Cediranib.
Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Cediranib.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with Cediranib.
FollitropinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Cediranib.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Cediranib.
LiothyronineThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Cediranib.
LiotrixThe therapeutic efficacy of Liotrix can be decreased when used in combination with Cediranib.
MethimazoleThe therapeutic efficacy of Methimazole can be decreased when used in combination with Cediranib.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Cediranib maleate68AYS9A614857036-77-2JRMGHBVACUJCRP-BTJKTKAUSA-N
International/Other Brands
Recentin

Categories

ATC Codes
L01XE32 — Cediranib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Quinazolines / Indoles / Anisoles / Alkyl aryl ethers / Substituted pyrroles / Pyrimidines and pyrimidine derivatives / N-alkylpyrrolidines / Aryl fluorides / Heteroaromatic compounds / Trialkylamines
show 4 more
Substituents
Alkyl aryl ether / Amine / Anisole / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Diaryl ether / Diazanaphthalene
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
NQU9IPY4K9
CAS number
288383-20-0
InChI Key
XXJWYDDUDKYVKI-UHFFFAOYSA-N
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
IUPAC Name
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
SMILES
COC1=CC2=C(C=C1OCCCN1CCCC1)N=CN=C2OC1=C(F)C2=C(NC(C)=C2)C=C1

References

General References
  1. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jurgensmeier JM, Ogilvie DJ: AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. [PubMed:15899831]
PubChem Compound
9933475
PubChem Substance
175426860
ChemSpider
8109103
BindingDB
50331096
ChEBI
94782
ChEMBL
CHEMBL491473
ZINC
ZINC000003948085
Wikipedia
AZD2171

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentFallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Fallopian Tube Undifferentiated Carcinoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Tumor / Ovarian Seromucinous Carcinoma / Ovarian Serous Tumor / Ovarian Transitional Cell Carcinoma / Ovarian Undifferentiated Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Endometrioid Adenocarcinoma / Recurrent Primary Peritoneal Carcinoma1
3CompletedTreatmentLung Cancers1
3CompletedTreatmentMetastatic Colorectal Cancer (MCRC)1
3CompletedTreatmentRecurrent Glioblastoma1
3RecruitingTreatmentOvarian Cancer1
3Unknown StatusTreatmentOvarian Cancer1
2Active Not RecruitingTreatmentAdult Glioblastoma / Adult Gliosarcoma1
2Active Not RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS)2
2Active Not RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS) / Alveolar Soft-part Sarcoma1
2Active Not RecruitingTreatmentCastration-Resistant Prostate Carcinoma / Metastatic Hormone Refractory Prostate Cancer / Metastatic Malignant Neoplasm in the Bone / Prostate Adenocarcinoma With Neuroendocrine Differentiation / Prostate Small Cell Carcinoma / Stage IV Prostate Adenocarcinoma AJCC v71

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0155 mg/mLALOGPS
logP3.77ALOGPS
logP4.13ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)16.59ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.5 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity125.16 m3·mol-1ChemAxon
Polarizability48.77 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.972
Caco-2 permeable+0.5919
P-glycoprotein substrateSubstrate0.6286
P-glycoprotein inhibitor IInhibitor0.7308
P-glycoprotein inhibitor IIInhibitor0.8118
Renal organic cation transporterInhibitor0.6936
CYP450 2C9 substrateNon-substrate0.8505
CYP450 2D6 substrateNon-substrate0.5395
CYP450 3A4 substrateSubstrate0.7607
CYP450 1A2 substrateInhibitor0.6053
CYP450 2C9 inhibitorNon-inhibitor0.5716
CYP450 2D6 inhibitorNon-inhibitor0.6498
CYP450 2C19 inhibitorInhibitor0.7982
CYP450 3A4 inhibitorInhibitor0.6267
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.922
Ames testNon AMES toxic0.641
CarcinogenicityNon-carcinogens0.9197
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5985 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7652
hERG inhibition (predictor II)Inhibitor0.8887
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jurgensmeier JM, Ogilvie DJ: AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. [PubMed:15899831]

Drug created on October 18, 2007 14:00 / Updated on June 12, 2020 10:52

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