This drug entry is a stub and has not been fully annotated. It was added on October 20, 2016 and is scheduled to be annotated soon.

Identification
NameTesevatinib
Accession NumberDB11973  (DB05007)
TypeSmall Molecule
GroupsInvestigational
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
Product Ingredients Not Available
ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIF6XM2TN5A1
CAS number781613-23-8
WeightAverage: 491.39
Monoisotopic: 490.1338596
Chemical FormulaC24H25Cl2FN4O2
InChI KeyHVXKQKFEHMGHSL-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
IndicationNot yet annotated
PharmacodynamicsNot yet annotated
Mechanism of actionTesevatinib 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Pro-epidermal growth factorProteinunknownNot AvailableHumanP01133 details
Ephrin type-B receptor 4ProteinunknownNot AvailableHumanP54760 details
Receptor tyrosine-protein kinase erbB-2ProteinunknownNot AvailableHumanP04626 details
Related Articles
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancers2
1RecruitingTreatmentPolycystic Kidney, Autosomal Recessive1
1WithdrawnTreatmentCancer, Breast / Cancers / Non-Small-Cell Lung Cancer (NSCLC)1
1WithdrawnTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
1, 2Active Not RecruitingTreatmentHER-2 Positive Breast Cancer / Metastatic Malignant Neoplasm to Brain1
1, 2Active Not RecruitingTreatmentPolycystic Kidney, Autosomal Dominant1
2Active Not RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
2CompletedTreatmentNon-Small-Cell Lung Cancer (NSCLC)1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2RecruitingTreatmentGlioblastomas / Neoplasms, Brain / Recurrent Glioblastoma1
2RecruitingTreatmentLeptomeningeal Metastases / Metastatic Brain Tumors / Non-Small-Cell Lung Carcinoma (NSCLC)1
3TerminatedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
Properties
StateNot Available
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazanaphthalenes
Sub ClassBenzodiazines
Direct ParentQuinazolinamines
Alternative ParentsAniline and substituted anilines / Anisoles / Dichlorobenzenes / Alkyl aryl ethers / Aminopyrimidines and derivatives / Fluorobenzenes / Aryl chlorides / N-alkylpyrrolidines / Imidolactams / Aryl fluorides
SubstituentsQuinazolinamine / Anisole / 1,2-dichlorobenzene / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Chlorobenzene / Fluorobenzene / Halobenzene / Aryl chloride
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro (PubMe...
Gene Name:
EGF
Uniprot ID:
P01133
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 signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cog...
Gene Name:
EPHB4
Uniprot ID:
P54760
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, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-...
Gene Name:
ERBB2
Uniprot ID:
P04626
Molecular Weight:
137909.27 Da
Drug created on October 20, 2016 15:07 / Updated on June 24, 2017 13:37