Amuvatinib

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

Identification

Name
Amuvatinib
Accession Number
DB12742  (DB05216)
Type
Small Molecule
Groups
Investigational
Description

Amuvatinib has been used in trials studying the treatment of Solid Tumors and Small Cell Lung Carcinoma. Amuvatinib is an oral, selective multi-targeted tyrosine kinase inhibitor that suppresses c-MET, c-RET and the mutant forms of c-KIT, PDGFR and FLT3. Amuvatinib also suppresses Rad51 protein, a critical component of double-stranded DNA repair in cancer cells.

Structure
Thumb
Synonyms
Not Available
External IDs
HPK 56 / HPK-56 / HPK56 / MP 470 / MP-470 / MP470
Product Ingredients
IngredientUNIICASInChI Key
Amuvatinib hydrochloride14L8O2K12B1055986-67-8IKQFRXPMBGQJGE-UHFFFAOYSA-N
Categories
Not Available
UNII
SO9S6QZB4R
CAS number
850879-09-3
Weight
Average: 447.51
Monoisotopic: 447.13651073
Chemical Formula
C23H21N5O3S
InChI Key
FOFDIMHVKGYHRU-UHFFFAOYSA-N
InChI
InChI=1S/C23H21N5O3S/c32-23(24-12-15-5-6-18-19(11-15)30-14-29-18)28-9-7-27(8-10-28)22-21-20(25-13-26-22)16-3-1-2-4-17(16)31-21/h1-6,11,13H,7-10,12,14H2,(H,24,32)
IUPAC Name
N-[(2H-1,3-benzodioxol-5-yl)methyl]-4-{8-oxa-3,5-diazatricyclo[7.4.0.0^{2,7}]trideca-1(9),2(7),3,5,10,12-hexaen-6-yl}piperazine-1-carbothioamide
SMILES
S=C(NCC1=CC=C2OCOC2=C1)N1CCN(CC1)C1=NC=NC2=C1OC1=C2C=CC=C1

Pharmacology

Indication

Amuvatinib is a selective multi-targeted tyrosine kinase inhibitor that suppresses c-MET, c-RET and the mutant forms of c-KIT, PDGFR and FLT3. Amuvatinib also suppresses Rad51 protein, a critical component of double-stranded DNA repair in cancer cells.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UMast/stem cell growth factor receptor KitNot AvailableHuman
UHepatocyte growth factor receptorNot AvailableHuman
UProto-oncogene tyrosine-protein kinase receptor RetNot AvailableHuman
UPlatelet-derived growth factor receptor alphaNot AvailableHuman
UReceptor-type tyrosine-protein kinase FLT3Not AvailableHuman
UDNA repair protein RAD51 homolog 1Not AvailableHuman
Absorption

Orally 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
  1. Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K, Wisner L, Iorio M, Shakalya K, Garewal H, Nagle R, Bearss D: A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19. Epub 2007 Feb 26. [PubMed:17325667]
  2. Product Announcement [Link]
External Links
PubChem Compound
11282283
PubChem Substance
347828932
ChemSpider
9457280
ChEBI
91389
ChEMBL
CHEMBL2103851

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignant Diseases1
1CompletedTreatmentTumors, Solid1
2CompletedTreatmentSmall Cell Lung Carcinoma1

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 Solubility0.0741 mg/mLALOGPS
logP2.79ALOGPS
logP3.52ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)14.11ChemAxon
pKa (Strongest Basic)1.37ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area75.89 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity124.53 m3·mol-1ChemAxon
Polarizability47.82 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
Benzofurans / Benzodioxoles / Dialkylarylamines / Aminopyrimidines and derivatives / Imidolactams / Benzenoids / Heteroaromatic compounds / Furans / Thioureas / Oxacyclic compounds
show 4 more
Substituents
N-arylpiperazine / Benzodioxole / Benzofuran / Dialkylarylamine / Aminopyrimidine / Pyrimidine / Benzenoid / Imidolactam / Furan / Heteroaromatic compound
show 12 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 activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K, Wisner L, Iorio M, Shakalya K, Garewal H, Nagle R, Bearss D: A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19. Epub 2007 Feb 26. [PubMed:17325667]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name
MET
Uniprot ID
P08581
Uniprot Name
Hepatocyte growth factor receptor
Molecular Weight
155540.035 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Single-stranded dna-dependent atpase activity
Specific Function
Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double-stranded DNA and exhibits ...
Gene Name
RAD51
Uniprot ID
Q06609
Uniprot Name
DNA repair protein RAD51 homolog 1
Molecular Weight
36965.82 Da

Drug created on October 20, 2016 17:58 / Updated on December 01, 2017 17:35