CANERTINIB DIHYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H25ClFN5O3.2ClH
Molecular Weight	558.86
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.FC1=C(Cl)C=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)C=C)C=C23)C=C1

InChI

InChIKey=JZZFDCXSFTVOJY-UHFFFAOYSA-N

InChI=1S/C24H25ClFN5O3.2ClH/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);2*1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10753475 | https://www.ncbi.nlm.nih.gov/pubmed/11706399 | https://www.ncbi.nlm.nih.gov/pubmed/14730468 | http://adisinsight.springer.com/drugs/800012072

Canertinib or CI-1033 (N-[4-[N-(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide) is a pan-erbB tyrosine kinase inhibitor. It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Canertinib was under development by Pfizer Inc as a potential treatment for cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10753475	Inhibitor 8297	1.5 nM [IC50]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10753475	Inhibitor 8297	9.0 nM [IC50]
Receptor protein-tyrosine kinase erbB-4 12 Target ID: CHEMBL3009 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11706399	Inhibitor 8297	7.0 nM [IC50]
Receptor tyrosine-protein kinase erbB-3 4 Target ID: CHEMBL5838 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11706399	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17761977	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12138393 https://www.ncbi.nlm.nih.gov/pubmed/19294387	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16110019	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
337.5 mg 3 times / week multiple, intravenous (total daily dose) Highest studied dose Dose: 337.5 mg, 3 times / week Route: intravenous Route: multiple Dose: 337.5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	unhealthy n = 7 Health Status: unhealthy Condition: advanced nonhematologic malignancies Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	DLT: hypersensitivity reaction, diarrhea... Dose limiting toxicities: hypersensitivity reaction (grade 3, 2 patients) diarrhea (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16899614
500 mg 3 times / week multiple, intravenous (total daily dose) Highest studied dose Dose: 500 mg, 3 times / week Route: intravenous Route: multiple Dose: 500 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	unhealthy n = 3 Health Status: unhealthy Condition: advanced nonhematologic malignancies Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	DLT: Myalgia, syncope... Dose limiting toxicities: Myalgia (grade 3, 2 patients) syncope (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16899614
750 mg 1 times / day multiple, oral (total daily dose) Highest studied dose Dose: 750 mg, 1 times / day Route: oral Route: multiple Dose: 750 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	unhealthy n = 3 Health Status: unhealthy Condition: refractory cancer Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	DLT: emesis, rash... Other AEs: Diarrhea... Dose limiting toxicities: emesis (grade 2, 1 pt) rash (grade 2, 1 pt) mouth ulcer (grade 2, 1 pt) emesis (grade 3, 1 pt) Other AEs: Diarrhea (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/17505003
225 mg 3 times / week multiple, intravenous (total daily dose) MTD Dose: 225 mg, 3 times / week Route: intravenous Route: multiple Dose: 225 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	unhealthy n = 7 Health Status: unhealthy Condition: advanced nonhematologic malignancies Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/16899614	Other AEs: Dyspnea, Infection... Other AEs: Dyspnea (1 pt) Infection (3 patients) Thrombocytopenia (1 pt) Cutaneous toxicities (7 patients) Pain (2 patients) Asthenia (2 patients) Vasodilation (2 patients) Stomatitis (2 patients) Myalgia (2 patients) Vomiting (2 patients) Nausea (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16899614
650 mg 1 times / day multiple, oral (total daily dose) MTD Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	unhealthy n = 8 Health Status: unhealthy Condition: Refractory cancer Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	DLT: thrombocytopenia... Other AEs: Emesis, rash... Dose limiting toxicities: thrombocytopenia (grade 4, 1 pt) Other AEs: Emesis (grade 3, 1 pt) rash (grade 1-2, 7 patients) Hypersensitivity (grade 1-2, 3 patients) Mucositis (grade 1-2, 6 patients) Nausea (grade 1-2, 5 patients) iarrhea (grade 1-2, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/17505003
200 mg 1 times / day multiple, oral (total daily dose) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16110019	unhealthy n = 52 Health Status: unhealthy Condition: ovarian cancer Sex: F Food Status: UNKNOWN Population Size: 52 Sources: https://pubmed.ncbi.nlm.nih.gov/16110019	Disc. AE: Diarrhea... Other AEs: Abdominal pain, Asthenia... AEs leading to discontinuation/dose reduction: Diarrhea (13%) Other AEs: Abdominal pain (13%) Asthenia (13%) Sources: https://pubmed.ncbi.nlm.nih.gov/16110019
50 mg 1 times / day multiple, oral (total daily dose) Studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16110019	unhealthy n = 53 Health Status: unhealthy Condition: ovarian cancer Sex: F Food Status: UNKNOWN Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/16110019	Disc. AE: diarrhea, Abdominal pain... AEs leading to discontinuation/dose reduction: diarrhea (10%) Abdominal pain (10%) Asthenia (10%) Sources: https://pubmed.ncbi.nlm.nih.gov/16110019
50 mg 1 times / day multiple, oral (total daily dose) Studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	unhealthy n = 7 Health Status: unhealthy Condition: Refractory cancer Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/17505003
560 mg 1 times / day multiple, oral (total daily dose) Studied dose Dose: 560 mg, 1 times / day Route: oral Route: multiple Dose: 560 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	unhealthy n = 8 Health Status: unhealthy Condition: refractory cancer Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17505003	DLT: Hypersensitivity... Dose limiting toxicities: Hypersensitivity (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/17505003

AEs

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116239	https://www.001chemical.com/chem/search?q=DY116239
1PlusChem LLC	1P002XN0	https://www.1pchem.com/search?query=1P002XN0
1PlusChem LLC	1P00BD0U	https://www.1pchem.com/search?query=1P00BD0U
A2B Chem	AF29294	http://a2bchem.com/prod/AF29294
AChemBlock	Q70216	http://www.achemblock.com/catalogsearch/result/?q=Q70216
AK Scientific	3516AH	https://aksci.com/item_detail.php?cat=3516AH
AK Scientific	Y0252	https://aksci.com/item_detail.php?cat=Y0252
Ambeed	A239262	http://www.ambeed.com/search/Search.html?keyword=A239262
ApexBio Technology	A1845	https://www.apexbt.com/catalogsearch/result/?q=A1845
ApexBio Technology	A3276	https://www.apexbt.com/catalogsearch/result/?q=A3276
AstaTech	40737	http://astatechinc.com/CPSResult.php?CRNO=40737
AstaTech	41114	http://astatechinc.com/CPSResult.php?CRNO=41114
Axon MedChem	1433	https://www.axonmedchem.com/product/1433
BLD Pharm	BD119839	http://www.bldpharm.com/search/Search.html?keyword=BD119839
BLD Pharm	BD157893	http://www.bldpharm.com/search/Search.html?keyword=BD157893
BOC Sciences	267243-28-7	http://www.bocsci.com/description.asp?cas=267243-28-7
BOC Sciences	289499-45-2	http://www.bocsci.com/description.asp?cas=289499-45-2
BioSynth	Q-101362	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-101362
BioSynth	Q-200788	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-200788
Capot Chemical	22407	https://www.capotchem.com/search.do?q=22407
Cayman Chemical	12076	http://www.caymanchem.com/app/template/Product.vm/catalog/12076
Chem Scene	CS-0121	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0121
Chem Scene	CS-0263	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0263
ChemShuttle	101092	https://www.chemshuttle.com/catalogsearch/result/?q=101092
ChemShuttle	112899	https://www.chemshuttle.com/catalogsearch/result/?q=112899
Excenen	EX-A078	http://www.excenen.com/searchresultlist.php?id=EX-A078
Exclusive Chemistry	2258	http://www.exchemistry.com/chem-catalog/product-2258.html
Hairui	HR113818	http://www.hairuichem.com/en/product/search.do?q=HR113818
Hairui	HR144361	http://www.hairuichem.com/en/product/search.do?q=HR144361
KeyOrganics	AS-56189	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56189
KeyOrganics	AS-75065	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-75065
Lab Seeker	SC-22834	http://www.labseeker.com/search.php?keywords=SC-22834&category=0
Lab Seeker	SC-23744	http://www.labseeker.com/search.php?keywords=SC-23744&category=0
LabSeeker	SC-22834	http://www.labseeker.com/search.php?keywords=SC-22834&category=0
LabSeeker	SC-23744	http://www.labseeker.com/search.php?keywords=SC-23744&category=0
Matrix Scientific	143588	http://www.matrixscientific.com/143588.html
Matrix Scientific	147556	http://www.matrixscientific.com/147556.html
MedChem Express	HY-10367	https://www.medchemexpress.com/search.html?q=HY-10367A&ft=&fa=&fp=
MedChem Express	HY-10367A	https://www.medchemexpress.com/search.html?q=HY-10367A&ft=&fa=&fp=
MolPort	MolPort-006-170-085	https://www.molport.com/shop/molecule-link/MolPort-006-170-085
MolPort	MolPort-008-155-957	https://www.molport.com/shop/molecule-link/MolPort-008-155-957
Molcore	MC116239	http://www.molcore.com/CatMC116239.html
Molnova	M13886	https://www.molnova.com/en/serch-list.html?keywords=M13886
Molnova	M18334	https://www.molnova.com/en/serch-list.html?keywords=M18334
MuseChem	I002916	https://www.musechem.com/product/I002916.html
MuseChem	I002998	https://www.musechem.com/product/I002998.html
Ryan Scientific	Chidamide	https://ryansci.com/products?q=Chidamide&list_q=&search_type=exact
Selleck Chemicals	S1019	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1019
ShangHai Biochempartner	BCP01790	http://www.biochempartner.com/search_BCP01790
ShangHai Biochempartner	BCP01902	http://www.biochempartner.com/search_BCP01902
TargetMol	T2501	https://www.targetmol.com/search?keyword=T2501
TargetMol	T6136	https://www.targetmol.com/search?keyword=T6136
eMolecules	31430535	https://orderbb.emolecules.com/search/#?query=31430535
eMolecules	46018078	https://orderbb.emolecules.com/search/#?query=46018078
eMolecules	8779390	https://orderbb.emolecules.com/search/#?query=8779390
eNovation Chemicals	D372498	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372498&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D514545	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D514545&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4299844914	https://mcule.com/MCULE-4299844914/
mcule	MCULE-9046492091	https://mcule.com/MCULE-9046492091/

PubMed

Title	Date	PubMed
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.	2000 Apr 6	10753475
Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor.	2000 Dec 1	11121658
Potential benefits of the irreversible pan-erbB inhibitor, CI-1033, in the treatment of breast cancer.	2002 Jun	12138393
Increased bioavailability of intravenous versus oral CI-1033, a pan erbB tyrosine kinase inhibitor: results of a phase I pharmacokinetic study.	2006 Aug 1	16899614
Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.	2007 Mar	17405897
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378

Patents

Sample Use Guides

In Vivo Use Guide

According to the phase I pharmacokinetic study canertinib (CI-1033) was safely given i.v. up to 225 mg/dose on a thrice-weekly schedule, with evidence of antitumor activity. At equivalent doses, the bioavailability of i.v. CI-1033 is thrice that of the oral formulation.

Route of Administration: Other

In Vitro Use Guide

The effect of canertinib (CI-1033) on esophageal cancer cell proliferation was investigated in the TT, TE2, TE6 and TE10 cell lines. After one day of treatment with CI-1033 (0.1-5.0 nM) significant inhibition of cell growth was observed in all cell lines at all concentrations of CI-1033 examined. The dose of CI-1033 required to inhibit the cell growth was as low as 0.1 nM. The inhibitory effect of CI-1033 on cancer cell growth was dose- and time-dependent.

Name

Type

Language

CANERTINIB DIHYDROCHLORIDE

Official Name

English

N-[4-(3-Chloro-4-fluorophenyl)amino]-7-(3-morpholin-4-yl)propoxy]quinazolin-6-yl]prop-2-enamide dihydrochloride

Common Name

English

CANERTINIB DIHYDROCHLORIDE [USAN]

Common Name

English

CANERTINIB DIHYDROCHLORIDE [MI]

Common Name

English

PD-0183805-002B

Code

English

Canertinib dihydrochloride [WHO-DD]

Common Name

English

N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(3-(4-MORPHOLINYL)PROPOXY)-6-QUINAZOLINYL)-2-PROPENAMIDE DIHYDROCHLORIDE

Systematic Name

English

CI-1033

Code

English

2-PROPENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL) AMINO)-7-(3-(4-MORPHOLINYL)PROPOXY)-6-QUINAZOLINYL)-, DIHYDROCHLORIDE

Common Name

English

PD-0183805

Code

English

CANERTINIB HYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825