NAV

Cediranib

Identification

Generic Name
Cediranib
DrugBank Accession Number
DB04849
Background

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
3D
Similar Structures
Weight
Average: 450.5053
Monoisotopic: 450.206718955
Chemical Formula
C25H27FN4O3
Synonyms
  • Cediranib
External IDs
  • AZD-2171
  • AZD2171
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Pharmacology

Indication

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

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Contraindications & Blackbox Warnings
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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
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
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AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Cediranib.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Cediranib is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Cediranib is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Cediranib is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Cediranib is combined with Benzyl alcohol.
Food Interactions
Not Available

Products

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

Categories

ATC Codes
L01EK02 — 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
Affected organisms
  • Humans and other mammals

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. [Article]
PubChem Compound
9933475
PubChem Substance
175426860
ChemSpider
8109103
BindingDB
50331096
ChEBI
94782
ChEMBL
CHEMBL491473
ZINC
ZINC000003948085
Wikipedia
AZD2171

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentClear Cell Adenocarcinoma of the Fallopian Tubes / Fallopian Tube Transitional Cell Carcinoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Tumor / Ovarian Seromucinous Carcinoma / Ovarian Transitional Cell Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Endometrioid Adenocarcinoma / Recurrent Primary Peritoneal Carcinoma / Serous Ovarian Tumor / Undifferentiated Fallopian Tube Carcinoma / Undifferentiated Ovarian Carcinoma1
3CompletedTreatmentLung Cancer1
3CompletedTreatmentMetastatic Colorectal Cancer (CRC)1
3CompletedTreatmentRecurrent Glioblastoma1
3RecruitingTreatmentOvarian Cancer1

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/MSsplash10-0udi-0000900000-ccd4d67ed5009c3fa3be
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-002b-0102900000-47ea016f8866d7a6d71e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ue9-3103900000-e26a4b6f01f003c0efc1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0004900000-e2c530a943aa27f18dab
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0gx0-9303300000-6049f60efbedfb5fa2ca
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-0309200000-95cee54b1e04d066e538
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-200.5949
predicted
DeepCCS 1.0 (2019)
[M+H]+202.9529
predicted
DeepCCS 1.0 (2019)
[M+Na]+209.04605
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Vascular endothelial growth factor receptor 2
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. [Article]

Drug created at October 18, 2007 20:00 / Updated at January 14, 2023 19:03