Varlitinib

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

Identification

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Name
Varlitinib
Accession Number
DB05944  (DB12723)
Type
Small Molecule
Groups
Investigational
Description

Varlitinib is an oral, selective, reversible, small molecule tyrosine kinase inhibitor of both ErbB-2 (Her-2/neu) and EGFR. Over-expression of ErbB-2 and EGFR receptors in tumors is predictive of poor prognosis in cancer patients. Varlitinib has shown significant anti-tumor activity in preclinical models of human breast, lung, and epidermal carcinoma tumors.

Structure
Thumb
Synonyms
Not Available
External IDs
AR-00334543 / AR00334543 / ARRY-334543 / ARRY-543 / ASLAN-001 / ASLAN001
Categories
UNII
846Y8197W1
CAS number
845272-21-1
Weight
Average: 466.94
Monoisotopic: 466.0978727
Chemical Formula
C22H19ClN6O2S
InChI Key
UWXSAYUXVSFDBQ-CYBMUJFWSA-N
InChI
InChI=1S/C22H19ClN6O2S/c1-13-10-31-22(27-13)29-14-2-4-18-16(8-14)21(26-12-25-18)28-15-3-5-19(17(23)9-15)30-11-20-24-6-7-32-20/h2-9,12-13H,10-11H2,1H3,(H,27,29)(H,25,26,28)/t13-/m1/s1
IUPAC Name
N4-{3-chloro-4-[(1,3-thiazol-2-yl)methoxy]phenyl}-N6-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine
SMILES
C[C@@H]1COC(NC2=CC=C3N=CN=C(NC4=CC=C(OCC5=NC=CS5)C(Cl)=C4)C3=C2)=N1

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified).

Pharmacodynamics
Not Available
Mechanism of action

Varlitinib is an orally active, reversible, enzymatic and cellular inhibitor, with nanomolar potency, of the key growth factor receptor tyrosine kinases ErbB-2 and EGFR. The compound possesses improved physiochemical properties relative to compounds directed at these targets currently in clinical development, and provides superior exposure and equivalent or greater efficacy in animal models of human cancer. Currently, there is no single drug on the market that selectively inhibits both ErbB-2 and EGFR. Varlitinib, which concurrently inhibits the molecular targets of the drugs Herceptin(R) (ErbB-2) and Erbitux(R) (EGFR), may provide enhanced efficacy in the treatment of cancer patients.

TargetActionsOrganism
UReceptor tyrosine-protein kinase erbB-2Not AvailableHumans
UEpidermal growth factor receptorNot AvailableHumans
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
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
PubChem Compound
42642648
PubChem Substance
347827751
ChemSpider
25027380
BindingDB
50205268
ChEMBL
CHEMBL2103842

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentAdvanced or Metastatic Biliary Tract Cancer / Advanced or Metastatic Solid Tumors1
1CompletedTreatmentCancer, Advanced2
1CompletedTreatmentTumors, Solid1
1RecruitingTreatmentTumors, Solid1
1, 2RecruitingTreatmentAdvanced/ Metastatic Hepatocellular Carcinoma1
1, 2RecruitingTreatmentBiliary Tract Cancer1
1, 2RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentBiliary Tract Cancer1
2CompletedBasic ScienceCancer of Stomach / Cancer of the Stomach / Malignant Neoplasm of Stomach / Neoplasm, Gastric / Stomach Neoplasms1
2CompletedTreatmentAdvanced or Metastatic Cholangiocarcinoma / Cholangiocarcinomas1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2WithdrawnTreatmentAdvanced or Metastatic Biliary Tract Cancer1
2, 3Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
2, 3RecruitingTreatmentBiliary Tract Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0047 mg/mLALOGPS
logP4.46ALOGPS
logP4.67ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)17.09ChemAxon
pKa (Strongest Basic)4.64ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area93.55 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity124.18 m3·mol-1ChemAxon
Polarizability48.53 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
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
Phenoxy compounds / Phenol ethers / Aniline and substituted anilines / Alkyl aryl ethers / Aminopyrimidines and derivatives / Chlorobenzenes / Aryl chlorides / Imidolactams / Heteroaromatic compounds / Thiazoles
show 8 more
Substituents
Quinazolinamine / Phenoxy compound / Phenol ether / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

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
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da

Drug created on November 18, 2007 11:28 / Updated on June 04, 2019 06:20