Foretinib

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
Foretinib
DrugBank Accession Number
DB12307
Background

Foretinib has been used in trials studying the treatment of Cancer, Breast Cancer, Carcinoma, Renal Cell, Recurrent Breast Cancer, and Neoplasms, Head and Neck, among others. Foretinib is an orally available small molecule compound designed to target multiple RTKs implicated in the development, progression and spread of cancer. It inhibits the activation of MET, RON, ERK and AKT, decreased proliferation and increased apoptosis.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 632.6538
Monoisotopic: 632.24464125
Chemical Formula
C34H34F2N4O6
Synonyms
  • Foretinib
External IDs
  • EXEL-2880
  • GSK-089
  • GSK-1363089
  • GSK-1363089G
  • GSK089
  • GSK1363089
  • GSK1363089G
  • XL 880
  • XL-880
  • XL880

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Activation of MET by mutation is the causative factor in an inherited kidney cancer syndrome, hereditary papilliary renal cell carcinaoma. Mutational activation of MET has also been found in sporadic kidney cancer, lung carcinomas and head and neck carcinomas. MET is a key driver of tumor cell growth, motility, invasion, metastasis and angiogenesis. Foretinib has attractive pharmaceutical properties with high solubility and oral bioavailability and demonstrates nanomolar potency against its targets, VEGFR, MET, which translates to potent activity in cellular assays. In preclinical studies, Foretinib, developed as a balanced inhibitor of these receptor tyrosine kinases, potently inhibited both MET and VEGFR, including mutant activated forms of MET found in hereditary papillary renal carcinomas. The compound also demonstrated dose-dependent growth inhibition in tumor models of breast, colorectal, non-small cell lung cancer and glioblastoma and has been shown to cause substantial tumor regression in all models tested.

TargetActionsOrganism
UHepatocyte growth factorNot AvailableHumans
UVascular endothelial growth factor receptor 2Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Foretinib.
CarbimazoleThe therapeutic efficacy of Carbimazole can be decreased when used in combination with Foretinib.
FollitropinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Foretinib.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Foretinib.
LiothyronineThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Foretinib.
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Quinolines and derivatives / Anilides / Anisoles / N-arylamides / Phenoxy compounds / Alkyl aryl ethers / Fluorobenzenes / Aryl fluorides / Morpholines / Cyclopropanecarboxylic acids and derivatives
show 13 more
Substituents
Alkyl aryl ether / Amine / Amino acid or derivatives / Anilide / Anisole / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
81FH7VK1C4
CAS number
849217-64-7
InChI Key
CXQHYVUVSFXTMY-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N'1-[3-fluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
SMILES
COC1=C(OCCCN2CCOCC2)C=C2N=CC=C(OC3=CC=C(NC(=O)C4(CC4)C(=O)NC4=CC=C(F)C=C4)C=C3F)C2=C1

References

General References
Not Available
PubChem Compound
42642645
PubChem Substance
347828572
ChemSpider
24608641
BindingDB
50399540
ChEBI
91418
ChEMBL
CHEMBL1230609
ZINC
ZINC000043204048
PDBe Ligand
88Z
Wikipedia
Foretinib
PDB Entries
3lq8 / 5ia4 / 6i2y / 6sd9 / 6sdc

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHead and Neck Neoplasms1
2CompletedTreatmentNeoplasms, Gastrointestinal Tract1
2CompletedTreatmentRecurrent Breast Cancer1
2CompletedTreatmentRenal Cell Carcinoma (RCC)1
2WithdrawnTreatmentCancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00364 mg/mLALOGPS
logP4.78ALOGPS
logP4.66Chemaxon
logS-5.2ALOGPS
pKa (Strongest Acidic)13.18Chemaxon
pKa (Strongest Basic)6.88Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area111.25 Å2Chemaxon
Rotatable Bond Count12Chemaxon
Refractivity168.3 m3·mol-1Chemaxon
Polarizability64.65 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-2200139000-c3aed503412921cb2b00
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1300509000-b9f49fba4b4e5c2e63df
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-016r-7910502000-b1a20f199bf91080356b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-2503946000-39634bfaee528c696f10
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014l-9401002000-5189bbc17a4ee1c4a349
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0609301000-a559f9c9f916ae25a5e1
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-243.40619
predicted
DeepCCS 1.0 (2019)
[M+H]+245.23106
predicted
DeepCCS 1.0 (2019)
[M+Na]+250.8825
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the rec...
Gene Name
HGF
Uniprot ID
P14210
Uniprot Name
Hepatocyte growth factor
Molecular Weight
83133.115 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da

Enzymes

Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:
References
  1. Singh RP, Patel B, Kallender H, Ottesen LH, Adams LM, Cox DS: Population pharmacokinetics modeling and analysis of foretinib in adult patients with advanced solid tumors. J Clin Pharmacol. 2015 Oct;55(10):1184-92. doi: 10.1002/jcph.546. Epub 2015 Jul 7. [Article]

Drug created at October 20, 2016 21:53 / Updated at February 21, 2021 18:53