Tesevatinib
Identification
- Generic Name
- Tesevatinib
- DrugBank Accession Number
- DB11973
- Background
Tesevatinib has been used in trials studying the treatment of Cancer, Stomach Cancer, Brain Metastases, Esophageal Cancer, and Leptomeningeal Metastases, among others.
Tesevatinib is a potent inhibitor of multiple RTKs implicated in driving tumor cell proliferation and tumor vascularization (blood vessel formation). Tesevatinib inhibits the EGF, HER2, and VEGF RTKs, each of which is a target of currently approved cancer therapies. In addition, tesevatinib inhibits EphB4, an RTK that is highly expressed in many human tumors and plays a role in promoting angiogenesis. In a broad array of preclinical tumor models including breast, lung, colon and prostate cancer, XL647 demonstrated potent inhibition of tumor growth and causes tumor regression. In cell culture models, tesevatinib retains significant potency against mutant EGFRs that are resistant to current EGFR inhibitors.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 491.39
Monoisotopic: 490.1338596 - Chemical Formula
- C24H25Cl2FN4O2
- Synonyms
- Tesevatinib
- External IDs
- EXEL-7647
- KD-019
- KD-020
- KD019
- XL647
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Tesevatinib inhibits the EGF, HER2, and VEGF RTKs, each of which is a target of currently approved cancer therapies. In addition, tesevatinib inhibits EphB4, an RTK that is highly expressed in many human tumors and plays a role in promoting angiogenesis. In a broad array of preclinical tumor models including breast, lung, colon and prostate cancer, XL647 demonstrated potent inhibition of tumor growth and causes tumor regression. In cell culture models, tesevatinib retains significant potency against mutant EGFRs that are resistant to current EGFR inhibitors.
Target Actions Organism UPro-epidermal growth factor Not Available Humans UEphrin type-B receptor 4 Not Available Humans UReceptor tyrosine-protein kinase erbB-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
50-70 hours
- 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 Tesevatinib. Ambroxol The risk or severity of methemoglobinemia can be increased when Tesevatinib is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Tesevatinib is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Tesevatinib is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Tesevatinib is combined with Benzyl alcohol. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Quinazolinamines
- Alternative Parents
- Aniline and substituted anilines / Anisoles / Dichlorobenzenes / Alkyl aryl ethers / Aminopyrimidines and derivatives / Fluorobenzenes / Aryl chlorides / N-alkylpyrrolidines / Imidolactams / Aryl fluorides show 8 more
- Substituents
- 1,2-dichlorobenzene / Alkyl aryl ether / Amine / Aminopyrimidine / Aniline or substituted anilines / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide show 25 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- F6XM2TN5A1
- CAS number
- 781613-23-8
- InChI Key
- HVXKQKFEHMGHSL-QKDCVEJESA-N
- InChI
- InChI=1S/C24H25Cl2FN4O2/c1-31-9-14-5-13(6-15(14)10-31)11-33-21-8-19-16(7-20(21)32-2)24(29-12-28-19)30-18-4-3-17(25)22(26)23(18)27/h3-4,7-8,12-15H,5-6,9-11H2,1-2H3,(H,28,29,30)/t13-,14-,15+
- IUPAC Name
- 7-{[(3aR,5S,6aS)-2-methyl-octahydrocyclopenta[c]pyrrol-5-yl]methoxy}-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine
- SMILES
- COC1=C(OC[C@H]2C[C@H]3CN(C)C[C@H]3C2)C=C2N=CN=C(NC3=CC=C(Cl)C(Cl)=C3F)C2=C1
References
- General References
- Not Available
- External Links
- PubChem Compound
- 10458325
- PubChem Substance
- 347828296
- ChemSpider
- 32699556
- ChEMBL
- CHEMBL3544983
- ZINC
- ZINC000114456300
- Wikipedia
- Tesevatinib
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 3 Terminated Treatment Non-Small Cell Lung Carcinoma 1 2 Completed Treatment Autosomal Dominant Polycystic Kidney Disease (ADPKD) 1 2 Completed Treatment Brain Metastases / Metastatic Malignant Neoplasm to the Leptomeninges / Non-Small Cell Lung Cancer (NSCLC) 1 2 Completed Treatment Brain Neoplasm / High Grade Glioma: Glioblastoma (GBM) / Recurrent Glioblastoma 1 2 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 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 0.00276 mg/mL ALOGPS logP 5.51 ALOGPS logP 5.25 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 14.01 Chemaxon pKa (Strongest Basic) 9.84 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 59.51 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 127.76 m3·mol-1 Chemaxon Polarizability 51 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 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
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-fb1d44daaf034c63b1df Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0000900000-bc7404b2c0f3a71c52c8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0001900000-d1eed34c42410eef8492 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-1003900000-aefb90634d20fff48588 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-1903300000-f80f1c175b2b9913e360 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-003r-4900700000-b5d2273de51144c80b58 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 203.17192 predictedDeepCCS 1.0 (2019) [M+H]+ 205.56749 predictedDeepCCS 1.0 (2019) [M+Na]+ 211.48001 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transmembrane receptor protein tyrosine kinase activator activity
- Specific Function
- EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in ...
- Gene Name
- EGF
- Uniprot ID
- P01133
- Uniprot Name
- Pro-epidermal growth factor
- Molecular Weight
- 133993.12 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The...
- Gene Name
- EPHB4
- Uniprot ID
- P54760
- Uniprot Name
- Ephrin type-B receptor 4
- Molecular Weight
- 108269.26 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
- Gene Name
- ERBB2
- Uniprot ID
- P04626
- Uniprot Name
- Receptor tyrosine-protein kinase erbB-2
- Molecular Weight
- 137909.27 Da
Drug created at October 20, 2016 21:07 / Updated at January 14, 2023 19:02