canertinib   Click here for help

GtoPdb Ligand ID: 5675

Synonyms: CI 1033 | CI-1033 | PD 183805 dihydrochloride [6]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Canertinib is an irreversible inhibitor which blocks signal transduction through all four members of the erbB family [1].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 88.61
Molecular weight 485.16
XLogP 3.08
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)Nc1cc2c(ncnc2cc1OCCCN1CCOCC1)Nc1ccc(c(c1)Cl)F
Isomeric SMILES C=CC(=O)Nc1cc2c(ncnc2cc1OCCCN1CCOCC1)Nc1ccc(c(c1)Cl)F
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)
InChI Key OMZCMEYTWSXEPZ-UHFFFAOYSA-N
References
1. Allen LF, Lenehan PF, Eiseman IA, Elliott WL, Fry DW. (2002)
Potential benefits of the irreversible pan-erbB inhibitor, CI-1033, in the treatment of breast cancer.
Semin Oncol, 29 (3 Suppl 11): 11-21. [PMID:12138393]
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
3. Nordigården A, Zetterblad J, Trinks C, Gréen H, Eliasson P, Druid P, Lotfi K, Rönnstrand L, Walz TM, Jönsson JI. (2011)
Irreversible pan-ERBB inhibitor canertinib elicits anti-leukaemic effects and induces the regression of FLT3-ITD transformed cells in mice.
Br J Haematol, 155 (2): 198-208. [PMID:21848891]
4. Rao GS, Murray S, Ethier SP. (2000)
Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor.
Int J Radiat Oncol Biol Phys, 48 (5): 1519-28. [PMID:11121658]
5. Rixe O, Franco SX, Yardley DA, Johnston SR, Martin M, Arun BK, Letrent SP, Rugo HS. (2009)
A randomized, phase II, dose-finding study of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in patients with pretreated metastatic breast cancer.
Cancer Chemother Pharmacol, 64 (6): 1139-48. [PMID:19294387]
6. Smaill JB, Rewcastle GW, Loo JA, Greis KD, Chan OH, Reyner EL, Lipka E, Showalter HD, Vincent PW, Elliott WL et al.. (2000)
Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
J Med Chem, 43 (7): 1380-97. [PMID:10753475]
7. Trinks C, Severinsson EA, Holmlund B, Gréen A, Gréen H, Jönsson JI, Hallbeck AL, Walz TM. (2011)
The pan-ErbB tyrosine kinase inhibitor canertinib induces caspase-mediated cell death in human T-cell leukemia (Jurkat) cells.
Biochem Biophys Res Commun, 410 (3): 422-7. [PMID:21669187]
8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]