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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:29 UTC
HMDB IDHMDB14421
Secondary Accession NumbersNone
Metabolite Identification
Common NameAmsacrine
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. [PubChem]
Structure
Thumb
Synonyms
ValueSource
4'-(9-acridinylamino)-3'-MethoxymethanesulfonanilideChEBI
4'-(9-acridinylamino)Methanesulfon-m-anisidideChEBI
4'-(9-acridinylamino)Methanesulfon-meta-anisidideChEBI
4'-(9-acridinylamino)Methanesulphon-m-anisidideChEBI
AmsacrinaChEBI
AmsacrinumChEBI
MAMSAChEBI
4'-(9-acridinylamino)-3'-MethoxymethanesulphonanilideGenerator
4'-(9-acridinylamino)Methanesulphon-meta-anisidideGenerator
Acridinyl anisidideHMDB
m-AMSAHMDB
Chemical FormulaC21H19N3O3S
Average Molecular Weight393.459
Monoisotopic Molecular Weight393.114712179
IUPAC NameN-{4-[(acridin-9-yl)amino]-3-methoxyphenyl}methanesulfonamide
Traditional Nameamsacrine
CAS Registry Number51264-14-3
SMILES
COC1=C(NC2=C3C=CC=CC3=NC3=CC=CC=C23)C=CC(NS(C)(=O)=O)=C1
InChI Identifier
InChI=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
DescriptionThis compound 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
  • Aminoquinoline
  • Sulfanilide
  • Methoxyaniline
  • Methoxybenzene
  • Substituted aniline
  • Phenol ether
  • Anisole
  • Aniline
  • Aminopyridine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Secondary amine
  • Ether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents
  • Intercalating Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point234 - 236 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.17e-03 g/LNot Available
LogP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0032 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity107.69 m3·mol-1ChemAxon
Polarizability41.65 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00276
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00276
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00276
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2094
KEGG Compound IDC01553
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAmsacrine
NuGOwiki LinkHMDB14421
Metagene LinkHMDB14421
METLIN IDNot Available
PubChem Compound2179
PDB IDNot Available
ChEBI ID2687
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. BC Cancer Agency [Link]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in ion channel activity
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). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular weight:
126653.5
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 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
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:
TOP2A
Uniprot ID:
P11388
Molecular weight:
174383.9
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 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [14985103 ]