Amsacrine (T3D4674)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-09-11 02:04:22 UTC
Update Date2014-12-24 20:26:54 UTC
Accession NumberT3D4674
Identification
Common NameAmsacrine
ClassSmall Molecule
DescriptionAminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects.
Compound Type
  • Amide
  • Antineoplastic Agent
  • Drug
  • Ether
  • Intercalating Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
4'-(9-Acridinylamino)-3'-methoxymethanesulfonanilide
4'-(9-Acridinylamino)methanesulfon-m-anisidide
4'-(9-Acridinylamino)methanesulfon-meta-anisidide
4'-(9-Acridinylamino)methanesulphon-m-anisidide
Acridinyl Anisidide
Amekrin
AMSA P-D
Amsidine
Amsidyl
M-AMSA
MAMSA
Chemical FormulaC21H19N3O3S
Average Molecular Mass393.459 g/mol
Monoisotopic Mass393.115 g/mol
CAS Registry Number51264-14-3
IUPAC NameN-{4-[(acridin-9-yl)amino]-3-methoxyphenyl}methanesulfonamide
Traditional Nameamsacrine
SMILESCOC1=C(C=CC(NS(C)(=O)=O)=C1)N=C1C2=CC=CC=C2NC2=CC=CC=C12
InChI IdentifierInChI=1S/C21H19N3O3S/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21/h3-13,24H,1-2H3,(H,22,23)
InChI KeyInChIKey=XCPGHVQEEXUHNC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassBenzoquinolines
Direct ParentAcridines
Alternative Parents
Substituents
  • Acridine
  • 4-aminoquinoline
  • Aminoquinoline
  • Sulfanilide
  • Aminophenyl ether
  • Methoxyaniline
  • Phenoxy compound
  • Anisole
  • Phenol ether
  • Methoxybenzene
  • Aniline or substituted anilines
  • Alkyl aryl ether
  • Aminopyridine
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Organosulfonic acid amide
  • Organic sulfonic acid amide
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Azacycle
  • Ether
  • Secondary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point235°C
Boiling PointNot Available
Solubility<1 mg/mL
LogP3.8
Predicted Properties
PropertyValueSource
Water Solubility0.0032 g/LALOGPS
logP4.66ALOGPS
logP3.16ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)10.82ChemAxon
pKa (Strongest Basic)8.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area80.32 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity107.69 m³·mol⁻¹ChemAxon
Polarizability41.65 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-02di-0019000000-7fcad477b7be592787132017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0007-0039000000-a2af4673e9da0eaf58582016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0092000000-8a23bcbe428e910816932016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000t-0090000000-3aca95179e2c583051c02016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-002f-5009000000-746720e7c744fadf47632016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9013000000-3e03298b63d7bfc80bf02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-630f95bbb2b03fc262f62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-e9cf7bbf444e4e4947d92021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0009000000-998445f6c8ead946b5872021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01pt-0898000000-b5849c315c2f06cf19a92021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-4dca3821da1c28bc99c32021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004l-4019000000-c3abc35c5eb7fd25ce6e2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-057i-9264000000-0de95adfd752b07865e42021-09-22View Spectrum
Toxicity Profile
Route of ExposurePoorly absorbed.
Mechanism of ToxicityAmsacrine binds to DNA through intercalation and external binding. It has a base specificity for A-T pairs. Rapidly dividing cells are two to four times more sensitive to amsacrine than are resting cells. Amsacrine appears to cleave DNA by inducing double stranded breaks. Amsacrine also targets and inhibits topoisomerase II. Cytotoxicity is greatest during the S phase of the cell cycle when topoisomerase levels are at a maximum.
MetabolismExtensive, primarily hepatic, converted to glutathione conjugate. Half Life: 8-9 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (2)
Uses/SourcesFor treatment of acute myeloid leukaemia.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include nausea and vomiting, diarrhea, some cardiotoxicity (rarely).
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00276
HMDB IDHMDB14421
PubChem Compound ID2179
ChEMBL IDCHEMBL43
ChemSpider ID2094
KEGG IDC01553
UniProt IDNot Available
OMIM ID
ChEBI ID2687
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAmsacrine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Link [Link]
  2. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. DNA topoisomerase 2-alpha
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 segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Finlay GJ, Atwell GJ, Baguley BC: Inhibition of the action of the topoisomerase II poison amsacrine by simple aniline derivatives: evidence for drug-protein interactions. Oncol Res. 1999;11(6):249-54. [10691026 ]
  2. Ferlin MG, Marzano C, Chiarelotto G, Baccichetti F, Bordin F: Synthesis and antiproliferative activity of some variously substituted acridine and azacridine derivatives. Eur J Med Chem. 2000 Sep;35(9):827-37. [11006484 ]
  3. Matsumoto Y, Takano H, Kunishio K, Nagao S, Fojo T: Hypophosphorylation of topoisomerase IIalpha in etoposide (VP-16)-resistant human carcinoma cell lines associated with carboxy-terminal truncation. Jpn J Cancer Res. 2001 Jul;92(7):799-805. [11473732 ]
  4. Lee MS, Wang JC, Beran M: Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. J Mol Biol. 1992 Feb 20;223(4):837-43. [1311390 ]
  5. Nitiss JL, Liu YX, Harbury P, Jannatipour M, Wasserman R, Wang JC: Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II. Cancer Res. 1992 Aug 15;52(16):4467-72. [1322791 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Arimondo P, Boukarim C, Bailly C, Dauzonne D, Monneret C: Design of two etoposide-amsacrine conjugates: topoisomerase II and tubuline polymerization inhibition and relation to cytotoxicity. Anticancer Drug Des. 2000 Dec;15(6):413-21. [11716434 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Gabelica V, Rosu F, De Pauw E, Antoine R, Tabarin T, Broyer M, Dugourd P: Electron photodetachment dissociation of DNA anions with covalently or noncovalently bound chromophores. J Am Soc Mass Spectrom. 2007 Nov;18(11):1990-2000. Epub 2007 Aug 22. [17900923 ]
  4. Capranico G, Guano F, Moro S, Zagotto G, Sissi C, Gatto B, Zunino F, Menta E, Palumbo M: Mapping drug interactions at the covalent topoisomerase II-DNA complex by bisantrene/amsacrine congeners. J Biol Chem. 1998 May 22;273(21):12732-9. [9582297 ]
Target Details
3. Potassium voltage-gated channel subfamily H member 2
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Thomas D, Hammerling BC, Wu K, Wimmer AB, Ficker EK, Kirsch GE, Kochan MC, Wible BA, Scholz EP, Zitron E, Kathofer S, Kreye VA, Katus HA, Schoels W, Karle CA, Kiehn J: Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94. Epub 2004 May 17. [15148258 ]