Amonafide

Identification

Name
Amonafide
Accession Number
DB05022
Type
Small Molecule
Groups
Investigational
Description

Amonafide is a substance that is being studied in the treatment of cancer. It belongs to the families of drugs called topoisomerase inhibitors and intercalating agents.

Structure
Thumb
Synonyms
Not Available
External IDs
NSC-308847
International/Other Brands
Quinamed
Categories
UNII
1Q8D39N37L
CAS number
69408-81-7
Weight
Average: 283.3251
Monoisotopic: 283.132076803
Chemical Formula
C16H17N3O2
InChI Key
UPALIKSFLSVKIS-UHFFFAOYSA-N
InChI
InChI=1S/C16H17N3O2/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21/h3-5,8-9H,6-7,17H2,1-2H3
IUPAC Name
11-amino-3-[2-(dimethylamino)ethyl]-3-azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-2,4-dione
SMILES
CN(C)CCN1C(=O)C2=CC=CC3=CC(N)=CC(C1=O)=C23

Pharmacology

Indication

Investigated for use/treatment in breast cancer, ovarian cancer, and prostate cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML.

TargetActionsOrganism
UDNA topoisomerase 2-alphaNot AvailableHuman
UDNA topoisomerase 2-betaNot AvailableHuman
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
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Amonafide.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Amonafide.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Amonafide.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Amonafide.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Amonafide.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Amonafide.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Amonafide.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Amonafide.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Amonafide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Amonafide.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Amonafide.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Amonafide.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Amonafide.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Amonafide.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Amonafide.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Amonafide.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Amonafide.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Amonafide.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Amonafide.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
50515
PubChem Substance
175426932
ChemSpider
45804
BindingDB
50033894
ChEBI
94661
ChEMBL
CHEMBL428676

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3Unknown StatusTreatmentSecondary Acute Myeloid Leukemia (Secondary AML, sAML)1

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 Solubility0.764 mg/mLALOGPS
logP0.9ALOGPS
logP1.1ChemAxon
logS-2.6ALOGPS
pKa (Strongest Basic)8.52ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area66.64 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity83.38 m3·mol-1ChemAxon
Polarizability30.1 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9784
Blood Brain Barrier+0.9724
Caco-2 permeable+0.6097
P-glycoprotein substrateSubstrate0.7806
P-glycoprotein inhibitor INon-inhibitor0.7457
P-glycoprotein inhibitor IINon-inhibitor0.7632
Renal organic cation transporterNon-inhibitor0.5063
CYP450 2C9 substrateNon-substrate0.8545
CYP450 2D6 substrateNon-substrate0.557
CYP450 3A4 substrateSubstrate0.705
CYP450 1A2 substrateInhibitor0.8204
CYP450 2C9 inhibitorNon-inhibitor0.8706
CYP450 2D6 inhibitorNon-inhibitor0.8765
CYP450 2C19 inhibitorNon-inhibitor0.8722
CYP450 3A4 inhibitorNon-inhibitor0.8756
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8379
Ames testNon AMES toxic0.5244
CarcinogenicityNon-carcinogens0.9172
BiodegradationNot ready biodegradable0.9847
Rat acute toxicity2.4943 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.895
hERG inhibition (predictor II)Inhibitor0.6327
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 isoquinolones and derivatives. These are aromatic polycyclic compounds containing a ketone bearing isoquinoline moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoquinolines and derivatives
Sub Class
Isoquinolones and derivatives
Direct Parent
Isoquinolones and derivatives
Alternative Parents
Naphthalenes / N-substituted carboxylic acid imides / Trialkylamines / Amino acids and derivatives / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Isoquinolone / Naphthalene / Carboxylic acid imide, n-substituted / Benzenoid / Carboxylic acid imide / Amino acid or derivatives / Tertiary aliphatic amine / Tertiary amine / Carboxylic acid derivative / Azacycle
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein kinase c binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name
TOP2B
Uniprot ID
Q02880
Uniprot Name
DNA topoisomerase 2-beta
Molecular Weight
183265.825 Da

Drug created on October 21, 2007 16:23 / Updated on November 09, 2017 03:50