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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 of FORETINIB

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.86 nM [IC50]
0.4 nM [IC50]
1.1 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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: 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: Page: p.745
DLT: Hypertension, Dehydration...
Dose limiting toxicities:
Hypertension (grade 3, 33.3%)
Dehydration (grade 3, 33.3%)
Sources: 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: 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: Page: p.745
Disc. AE: Left ventricular dysfunction...
AEs leading to
discontinuation/dose reduction:
Left ventricular dysfunction (grade 3, 4%)
Sources: Page: p.745
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: Page: p.745
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
2012 Dec 27
Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety.
2013 Jun
Patents

Sample Use Guides

240 mg/day, for 5 days every 2 weeks or daily - 80 mg per day.
Route of Administration: Oral
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 GMT 2023
Edited
by admin
on Sat Dec 16 16:58:54 GMT 2023
Record UNII
81FH7VK1C4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FORETINIB
INN   USAN   WHO-DD  
INN   USAN  
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
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
Code System Code Type Description
PUBCHEM
42642645
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
USAN
WW-14
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
DRUG BANK
DB12307
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
ChEMBL
CHEMBL1230609
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
EVMPD
SUB178744
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
NCI_THESAURUS
C80058
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
CAS
849217-64-7
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
WIKIPEDIA
FORETINIB
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
FDA UNII
81FH7VK1C4
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
SMS_ID
100000164345
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
INN
9202
Created by admin on Sat Dec 16 16:58:54 GMT 2023 , Edited by admin on Sat Dec 16 16:58:54 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY