Explore a selection of our essential drug information below, or:
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
Structure for Cediranib (DB04849)
- Weight
- Average: 450.5053
Monoisotopic: 450.206718955 - Chemical Formula
- C25H27FN4O3
- Synonyms
- Cediranib
- 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.
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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.
Target Actions Organism AVascular endothelial growth factor receptor 2 inhibitorHumans - 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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Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Cediranib. Ambroxol The risk or severity of methemoglobinemia can be increased when Cediranib is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Cediranib is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Cediranib is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Cediranib is combined with Benzyl alcohol. - Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Cediranib maleate 68AYS9A614 857036-77-2 JRMGHBVACUJCRP-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
- 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]
- External Links
- PubChem Compound
- 9933475
- PubChem Substance
- 175426860
- ChemSpider
- 8109103
- BindingDB
- 50331096
- ChEBI
- 94782
- ChEMBL
- CHEMBL491473
- ZINC
- ZINC000003948085
- Wikipedia
- AZD2171
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
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
Property Value Source Water Solubility 0.0155 mg/mL ALOGPS logP 3.77 ALOGPS logP 4.13 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 16.59 Chemaxon pKa (Strongest Basic) 9.14 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 72.5 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 125.16 m3·mol-1 Chemaxon Polarizability 48.77 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9928 Blood Brain Barrier + 0.972 Caco-2 permeable + 0.5919 P-glycoprotein substrate Substrate 0.6286 P-glycoprotein inhibitor I Inhibitor 0.7308 P-glycoprotein inhibitor II Inhibitor 0.8118 Renal organic cation transporter Inhibitor 0.6936 CYP450 2C9 substrate Non-substrate 0.8505 CYP450 2D6 substrate Non-substrate 0.5395 CYP450 3A4 substrate Substrate 0.7607 CYP450 1A2 substrate Inhibitor 0.6053 CYP450 2C9 inhibitor Non-inhibitor 0.5716 CYP450 2D6 inhibitor Non-inhibitor 0.6498 CYP450 2C19 inhibitor Inhibitor 0.7982 CYP450 3A4 inhibitor Inhibitor 0.6267 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.922 Ames test Non AMES toxic 0.641 Carcinogenicity Non-carcinogens 0.9197 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5985 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7652 hERG inhibition (predictor II) Inhibitor 0.8887
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0000900000-ccd4d67ed5009c3fa3be Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-002b-0102900000-47ea016f8866d7a6d71e Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0ue9-3103900000-e26a4b6f01f003c0efc1 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0004900000-e2c530a943aa27f18dab Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0gx0-9303300000-6049f60efbedfb5fa2ca Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-05fr-0309200000-95cee54b1e04d066e538 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.5949 predictedDeepCCS 1.0 (2019) [M+H]+ 202.9529 predictedDeepCCS 1.0 (2019) [M+Na]+ 209.04605 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC
- Specific Function
- Atp binding
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at October 18, 2007 20:00 / Updated at August 26, 2024 19:23