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
Structure for Foretinib (DB12307)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism UHepatocyte growth factor Not Available Humans UVascular endothelial growth factor receptor 2 Not Available Humans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Foretinib. Carbimazole The therapeutic efficacy of Carbimazole can be decreased when used in combination with Foretinib. Follitropin The therapeutic efficacy of Follitropin can be decreased when used in combination with Foretinib. Levothyroxine The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Foretinib. Liothyronine The 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
- External Links
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Head and Neck Neoplasms 1 2 Completed Treatment Neoplasms, Gastrointestinal Tract 1 2 Completed Treatment Recurrent Breast Cancer 1 2 Completed Treatment Renal Cell Carcinoma (RCC) 1 2 Withdrawn Treatment Cancer 1
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
Property Value Source Water Solubility 0.00364 mg/mL ALOGPS logP 4.78 ALOGPS logP 4.66 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 13.18 Chemaxon pKa (Strongest Basic) 6.88 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 111.25 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 168.3 m3·mol-1 Chemaxon Polarizability 64.65 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 243.40619 predictedDeepCCS 1.0 (2019) [M+H]+ 245.23106 predictedDeepCCS 1.0 (2019) [M+Na]+ 250.8825 predictedDeepCCS 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:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- 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