Tesevatinib

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

Identification

Name
Tesevatinib
Accession Number
DB11973  (DB05007)
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
  • TESEVATINIB
External IDs
EXEL-7647 / KD-019 / KD-020 / KD019 / XL647
Categories
UNII
F6XM2TN5A1
CAS number
781613-23-8
Weight
Average: 491.39
Monoisotopic: 490.1338596
Chemical Formula
C24H25Cl2FN4O2
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[[email protected]]2C[[email protected]]3CN(C)C[[email protected]]3C2)C=C2N=CN=C(NC3=CC=C(Cl)C(Cl)=C3F)C2=C1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
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 AvailableHuman
UEphrin type-B receptor 4Not AvailableHuman
UReceptor tyrosine-protein kinase erbB-2Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
32699556
ChEMBL
CHEMBL3544983

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancers2
1RecruitingTreatmentPolycystic Kidney, Autosomal Recessive1
1WithdrawnTreatmentCancer, Breast / Cancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1WithdrawnTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
1, 2Active Not RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
1, 2TerminatedTreatmentHER-2 Positive Breast Cancer / Metastatic Malignant Neoplasm to Brain1
2Active Not RecruitingTreatmentGlioblastomas / Neoplasms, Brain / Recurrent Glioblastoma1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
2RecruitingTreatmentLeptomeningeal Metastases / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1
2TerminatedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
3TerminatedTreatmentLung Cancer Non-Small Cell 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
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

Taxonomy

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
Quinazolinamine / Anisole / 1,2-dichlorobenzene / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Chlorobenzene / Fluorobenzene / Halobenzene / Aryl chloride
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
Human
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
Human
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 15:07 / Updated on October 02, 2017 06:24