Canertinib

Identification

Name
Canertinib
Accession Number
DB05424
Type
Small Molecule
Groups
Investigational
Description

Canertinib is a pan-erbB tyrosine kinase inhibitor which work against esophageal squamous cell carcinoma in vitro and in vivo. Canertinib treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET.

Structure
Thumb
Synonyms
Not Available
External IDs
PD-183805
Product Ingredients
IngredientUNIICASInChI Key
Canertinib dihydrochlorideICJ93X8X90289499-45-2JZZFDCXSFTVOJY-UHFFFAOYSA-N
Categories
UNII
C78W1K5ASF
CAS number
267243-28-7
Weight
Average: 485.938
Monoisotopic: 485.162995603
Chemical Formula
C24H25ClFN5O3
InChI Key
OMZCMEYTWSXEPZ-UHFFFAOYSA-N
InChI
InChI=1S/C24H25ClFN5O3/c1-2-23(32)30-21-13-17-20(14-22(21)34-9-3-6-31-7-10-33-11-8-31)27-15-28-24(17)29-16-4-5-19(26)18(25)12-16/h2,4-5,12-15H,1,3,6-11H2,(H,30,32)(H,27,28,29)
IUPAC Name
N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide
SMILES
FC1=C(Cl)C=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)C=C)C=C23)C=C1

Pharmacology

Indication

Investigated for use/treatment in breast cancer and lung cancer.

Pharmacodynamics
Not Available
Mechanism of action

CI-1033 effectively inhibits the growth of esophageal squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of both MAPK and AKT. Some studies suggest that CI-1033 holds significant clinical potential in esophageal cancer.

TargetActionsOrganism
UEpidermal growth factor receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Canertinib.
PropacetamolThe serum concentration of Propacetamol can be increased when it is combined with Canertinib.
Food Interactions
Not Available

References

General References
  1. Simon GR, Garrett CR, Olson SC, Langevin M, Eiseman IA, Mahany JJ, Williams CC, Lush R, Daud A, Munster P, Chiappori A, Fishman M, Bepler G, Lenehan PF, Sullivan DM: Increased bioavailability of intravenous versus oral CI-1033, a pan erbB tyrosine kinase inhibitor: results of a phase I pharmacokinetic study. Clin Cancer Res. 2006 Aug 1;12(15):4645-51. [PubMed:16899614]
  2. Sequist LV: Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Oncologist. 2007 Mar;12(3):325-30. [PubMed:17405897]
External Links
PubChem Compound
156414
PubChem Substance
175427000
ChemSpider
137741
BindingDB
4779
ChEBI
61399
ChEMBL
CHEMBL31965
Wikipedia
Canertinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNeoplasms, Breast1

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
logP4.09ALOGPS
logP3.9ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)12.54ChemAxon
pKa (Strongest Basic)6.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area88.61 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity130.55 m3·mol-1ChemAxon
Polarizability50.36 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9917
Blood Brain Barrier+0.9577
Caco-2 permeable-0.5685
P-glycoprotein substrateSubstrate0.6999
P-glycoprotein inhibitor IInhibitor0.9152
P-glycoprotein inhibitor IIInhibitor0.9592
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.8114
CYP450 2D6 substrateNon-substrate0.7455
CYP450 3A4 substrateSubstrate0.6732
CYP450 1A2 substrateNon-inhibitor0.5366
CYP450 2C9 inhibitorInhibitor0.5958
CYP450 2D6 inhibitorNon-inhibitor0.8724
CYP450 2C19 inhibitorInhibitor0.5504
CYP450 3A4 inhibitorInhibitor0.827
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8911
Ames testNon AMES toxic0.5465
CarcinogenicityNon-carcinogens0.8916
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7549 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5387
hERG inhibition (predictor II)Inhibitor0.8273
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
Aniline and substituted anilines / N-arylamides / Alkyl aryl ethers / Aminopyrimidines and derivatives / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides / Imidolactams / Morpholines
show 15 more
Substituents
Quinazolinamine / N-arylamide / Aniline or substituted anilines / Alkyl aryl ether / Halobenzene / Fluorobenzene / Aminopyrimidine / Chlorobenzene / Pyrimidine / Aryl chloride
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, monochlorobenzenes, quinazolines, morpholines (CHEBI:61399)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da

Drug created on November 18, 2007 11:24 / Updated on November 02, 2018 09:11