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Identification
NameCI-1033
Accession NumberDB05424
TypeSmall Molecule
GroupsInvestigational
Description

CI-1033 is a pan-erbB tyrosine kinase inhibitor which work against esophageal squamous cell carcinoma in vitro and in vivo. CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIINot Available
CAS numberNot Available
WeightAverage: 485.938
Monoisotopic: 485.162995603
Chemical FormulaC24H25ClFN5O3
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • N-arylamide
  • Halobenzene
  • Fluorobenzene
  • Chlorobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Oxazinane
  • Morpholine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationInvestigated for use/treatment in breast cancer and lung cancer.
PharmacodynamicsNot Available
Mechanism of actionCI-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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on ke...
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
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Drug created on November 18, 2007 11:24 / Updated on September 16, 2013 17:27