Tesevatinib

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

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
Thumb
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

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
UPro-epidermal growth factorNot AvailableHumans
UEphrin type-B receptor 4Not AvailableHumans
UReceptor tyrosine-protein kinase erbB-2Not AvailableHumans
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
Adverseeffects
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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
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Tesevatinib.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Tesevatinib.
CarbimazoleThe therapeutic efficacy of Carbimazole can be decreased when used in combination with Tesevatinib.
Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Tesevatinib.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with Tesevatinib.
FollitropinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Tesevatinib.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Tesevatinib.
LiothyronineThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Tesevatinib.
LiotrixThe therapeutic efficacy of Liotrix can be decreased when used in combination with Tesevatinib.
MethimazoleThe therapeutic efficacy of Methimazole can be decreased when used in combination with Tesevatinib.
Interactions
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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
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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
PubChem Compound
10458325
PubChem Substance
347828296
ChemSpider
32699556
ChEMBL
CHEMBL3544983
ZINC
ZINC000114456300
Wikipedia
Tesevatinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2Active Not RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
2CompletedTreatmentGlioblastoma Multiforme (GBM) / Neoplasms, Brain / Recurrent Glioblastoma1
2CompletedTreatmentLeptomeningeal Metastases / Non-Small Cell Lung Carcinoma (NSCLC) / Tumors Metastatic to Brain1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
2TerminatedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
1CompletedTreatmentAutosomal Recessive Polycystic Kidney Disease (ARPKD)1
1CompletedTreatmentMalignancies2
1RecruitingTreatmentB Cell Lymphoma (BCL) / B-cell Acute Lymphoblastic Leukemia1
1WithdrawnTreatmentBreast Cancer / Malignancies / Non-Small Cell Lung Carcinoma (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
PropertyValueSource
Water Solubility0.00276 mg/mLALOGPS
logP5.51ALOGPS
logP5.25ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)14.01ChemAxon
pKa (Strongest Basic)9.84ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.51 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity127.76 m3·mol-1ChemAxon
Polarizability51 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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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 on October 20, 2016 21:07 / Updated on February 21, 2021 18:53