FORETINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H34F2N4O6
Molecular Weight	632.6538
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OCCCN3CCOCC3)N=CC=C2OC4=C(F)C=C(NC(=O)C5(CC5)C(=O)NC6=CC=C(F)C=C6)C=C4

InChI

InChIKey=CXQHYVUVSFXTMY-UHFFFAOYSA-N

InChI=1S/C34H34F2N4O6/c1-43-30-20-25-27(21-31(30)45-16-2-13-40-14-17-44-18-15-40)37-12-9-28(25)46-29-8-7-24(19-26(29)36)39-33(42)34(10-11-34)32(41)38-23-5-3-22(35)4-6-23/h3-9,12,19-21H,2,10-11,13-18H2,1H3,(H,38,41)(H,39,42)

HIDE SMILES / InChI

Molecular Formula	C34H34F2N4O6
Molecular Weight	632.6538
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=428188
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800022245 | https://www.ncbi.nlm.nih.gov/pubmed/23213094 | http://www.exelixis.com/pipeline/xl880 | https://en.wikipedia.org/wiki/Foretinib

Foretinib is an orally available multikinase inhibitor that targets c-MET and VEGFR2 with high affinity, which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. Foretinib is an experimental drug candidate for the treatment of cancer. It was in Phase II trials for the treatment breast cancer, non-small cell lung cancer, gastric cancer, head and neck cancer and papillary renal-cell carcinoma. The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: http://www.exelixis.com/pipeline/xl880	Inhibitor 8297	0.86 nM [IC50]
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: http://www.exelixis.com/pipeline/xl880	Inhibitor 8297	0.4 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19808973	Inhibitor 8297	1.1 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: http://adisinsight.springer.com/trials/700055257	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/trials/700048569http://www.exelixis.com/pipeline/xl880	Primary	Phase II 1132	Unknown Approved Use Unknown
Gastric cancer 53 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23516391	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	DLT: Hypertension, Dehydration... Dose limiting toxicities: Hypertension (grade 3, 33.3%) Dehydration (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745
80 mg 1 times / day multiple, oral MTD Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	unhealthy, ADULT n = 25 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	Disc. AE: Left ventricular dysfunction... AEs leading to discontinuation/dose reduction: Left ventricular dysfunction (grade 3, 4%) Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745

AEs

AE	Significance	Dose	Population
Dehydration	grade 3, 33.3% DLT	120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745
Hypertension	grade 3, 33.3% DLT	120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745
Left ventricular dysfunction	grade 3, 4% Disc. AE	80 mg 1 times / day multiple, oral MTD Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745	unhealthy, ADULT n = 25 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/23054208 Page: p.745

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0038US	https://www.1pchem.com/search?query=1P0038US
AChemBlock	A-628	http://www.achemblock.com/catalogsearch/result/?q=A-628
AK Scientific	SYN1129	https://aksci.com/item_detail.php?cat=SYN1129
AK Scientific	W8766	https://aksci.com/item_detail.php?cat=W8766
Aceschem	ACF022966	https://www.aceschem.com/catalog/search.do?q=ACF022966
ApexBio Technology	A2974	https://www.apexbt.com/catalogsearch/result/?q=A2974
AstaTech	42016	http://astatechinc.com/CPSResult.php?CRNO=42016
Axon MedChem	1582	https://www.axonmedchem.com/product/1582
Capot Chemical	22993	https://www.capotchem.com/search.do?q=22993
Cayman Chemical	16249	http://www.caymanchem.com/app/template/Product.vm/catalog/16249
Chem Scene	CS-0153	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0153
Combi-Blocks	QJ-1646	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-1646
Excenen	EX-A050	http://www.excenen.com/searchresultlist.php?id=EX-A050
Exclusive Chemistry	2326	http://www.exchemistry.com/chem-catalog/product-2326.html
KeyOrganics	AS-16268	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16268
Matrix Scientific	125243	http://www.matrixscientific.com/125243.html
MedChem Express	HY-10338	https://www.medchemexpress.com/search.html?q=HY-10338&ft=&fa=&fp=
MolPort	MolPort-009-679-450	https://www.molport.com/shop/molecule-link/MolPort-009-679-450
Molnova	M16164	https://www.molnova.com/en/serch-list.html?keywords=M16164
MuseChem	I005091	https://www.musechem.com/product/I005091.html
ShangHai Biochempartner	BCP000276	http://www.biochempartner.com/search_BCP000276
ShangHai Biochempartner	BCP02231	http://www.biochempartner.com/search_BCP02231
Synthonix	14768	https://synthonix.com/catalogsearch/result/?q=14768
TargetMol	T3113	https://www.targetmol.com/search?keyword=T3113
Tetrahedron	TS89741	http://www.thsci.com/search.do?q=TS89741
eMolecules	32176468	https://orderbb.emolecules.com/search/#?query=32176468
eNovation Chemicals	D210803	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D210803&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7554935839	https://mcule.com/MCULE-7554935839/

PubMed

Title	Date	PubMed
		252160273
Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases.	2009 Oct 15	19808973
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
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.	2012 Dec 27	23098265
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.	2012 Jul 1	22751098
LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling.	2012 Mar 1	22241084
Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety.	2013 Jun	23644189

Patents

Sample Use Guides

In Vivo Use Guide

240 mg/day, for 5 days every 2 weeks or daily - 80 mg per day.

Route of Administration: Oral

In Vitro Use Guide

Gastric cancer cell lines MKN-45 and KATO-III, were found to be sensitive to foretinib (IC50 for MKN-45 and KATOIII, 8 nM and 30 nM, respectively).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:58:54 UTC 2023` Edited by `admin` on `Sat Dec 16 16:58:54 UTC 2023`
Record UNII	81FH7VK1C4
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FORETINIB

Official Name

English

GSK-1363089G

Code

English

EXEL-2880

Code

English

GSK1363089

Common Name

English

XL-880

Code

English

XL880

Code

English

1,1-CYCLOPROPANEDICARBOXAMIDE, N-(3-FLUORO-4-((6-METHOXY-7-(3-(4- MORPHOLINYL)PROPOXY)-4-QUINOLINYL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)-

Systematic Name

English

GSK1363089G

Code

English

Foretinib [WHO-DD]

Common Name

English

GSK089

Code

English

GSK-089

Code

English

GSK-1363089

Code

English

FORETINIB [USAN]

Common Name

English

N-(3-FLUORO-4-((6-METHOXY-7-(3-(MORPHOLIN-4-YL)PROPOXY)QUINOLIN-4-YL)OXY) PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE

Systematic Name

English

foretinib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967