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

Identification
NameAmuvatinib
Accession NumberDB12742  (DB05216)
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External IDs HPK 56 / HPK-56 / HPK56 / MP 470 / MP-470 / MP470
Product Ingredients
IngredientUNIICASInChI KeyDetails
Amuvatinib hydrochloride14L8O2K12B 1055986-67-8IKQFRXPMBGQJGE-UHFFFAOYSA-NDetails
ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
CategoriesNot Available
UNIISO9S6QZB4R
CAS number850879-09-3
WeightAverage: 447.51
Monoisotopic: 447.13651073
Chemical FormulaC23H21N5O3S
InChI KeyFOFDIMHVKGYHRU-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
PharmacodynamicsNot Available
Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
Mast/stem cell growth factor receptor KitProteinunknownNot AvailableHumanP10721 details
Hepatocyte growth factor receptorProteinunknownNot AvailableHumanP08581 details
Proto-oncogene tyrosine-protein kinase receptor RetProteinunknownNot AvailableHumanP07949 details
Platelet-derived growth factor receptor alphaProteinunknownNot AvailableHumanP16234 details
Receptor-type tyrosine-protein kinase FLT3ProteinunknownNot AvailableHumanP36888 details
DNA repair protein RAD51 homolog 1ProteinunknownNot AvailableHumanQ06609 details
Related Articles
Absorption

Orally available

Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignant Diseases1
1CompletedTreatmentTumors, Solid1
2Unknown StatusTreatmentSmall Cell Lung Carcinoma1
Properties
StateNot Available
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentN-arylpiperazines
Alternative ParentsBenzofurans / Benzodioxoles / Dialkylarylamines / Aminopyrimidines and derivatives / Imidolactams / Benzenoids / Heteroaromatic compounds / Furans / Thioureas / Oxacyclic compounds
SubstituentsN-arylpiperazine / Benzodioxole / Benzofuran / Dialkylarylamine / Aminopyrimidine / Pyrimidine / Benzenoid / Imidolactam / Furan / Heteroaromatic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
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 proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream sig...
Gene Name:
MET
Uniprot ID:
P08581
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 derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during in...
Gene Name:
RET
Uniprot ID:
P07949
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 chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for...
Gene Name:
PDGFRA
Uniprot ID:
P16234
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. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or...
Gene Name:
FLT3
Uniprot ID:
P36888
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 DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in...
Gene Name:
RAD51
Uniprot ID:
Q06609
Molecular Weight:
36965.82 Da
Drug created on October 20, 2016 17:58 / Updated on June 24, 2017 13:42