NAV

Amsacrine

Identification

Summary

Amsacrine is a cytotoxic agent used to induce remission in acute adult leukemia that is not adequately responsive to other agents.

Generic Name
Amsacrine
DrugBank Accession Number
DB00276
Background

Aminoacridine 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 393.459
Monoisotopic: 393.114712179
Chemical Formula
C21H19N3O3S
Synonyms
  • 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
  • Amsacrina
  • Amsacrine
  • Amsacrinum
  • m-AMSA
  • mAMSA
External IDs
  • CI-880
  • CL-880
  • NSC-156303
  • NSC-249992
  • SN-11841
  • SN-21429
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Pharmacology

Indication

For treatment of acute myeloid leukaemia.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofRefractory leukemia••••••••••••••••••••••• •••••••••••• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Amsacrine is an aminoacridine 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.

Mechanism of action

Amsacrine 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.

TargetActionsOrganism
ADNA
intercalation
Humans
ADNA topoisomerase 2-alpha
inhibitor
Humans
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Humans
UAlpha-1-acid glycoprotein 1Not AvailableHumans
USerum albuminNot AvailableHumans
Absorption

Poorly absorbed

Volume of distribution

Not Available

Protein binding

96-98%

Metabolism

Extensive, primarily hepatic, converted to glutathione conjugate.

Route of elimination

Not Available

Half-life

8-9 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include nausea and vomiting, diarrhea, some cardiotoxicity (rarely).

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbataceptThe risk or severity of adverse effects can be increased when Amsacrine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Amsacrine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Amsacrine.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Amsacrine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Amsacrine.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Amsacrine gluconateM4P91439UZ80277-07-2XXNAQBNJPZNRSZ-IFWQJVLJSA-N
Amsacrine hydrochlorideU66HX4K4CO54301-15-4WDISRLXRMMTXEV-UHFFFAOYSA-N
Amsacrine mesylate7LWQ0T63UA54301-16-5KIDGPIWSXHBPDH-UHFFFAOYSA-N
International/Other Brands
Amekrin / AMSA P-D / Amsidine / Amsidyl
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Amsa PdLiquid50 mg / mLIntravenousSearchlight Pharma Inc1983-12-31Not applicableCanada flag

Categories

ATC Codes
L01XX01 — Amsacrine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridines
Alternative Parents
4-aminoquinolines / Sulfanilides / Aminophenyl ethers / Methoxyanilines / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Aminopyridines and derivatives / Organosulfonamides
show 8 more
Substituents
4-aminoquinoline / Acridine / Alkyl aryl ether / Amine / Aminophenyl ether / Aminopyridine / Aminoquinoline / Aminosulfonyl compound / Aniline or substituted anilines / Anisole
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, sulfonamide, acridines (CHEBI:2687)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
00DPD30SOY
CAS number
51264-14-3
InChI Key
XCPGHVQEEXUHNC-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-{4-[(acridin-9-yl)amino]-3-methoxyphenyl}methanesulfonamide
SMILES
COC1=C(NC2=C3C=CC=CC3=NC3=CC=CC=C23)C=CC(NS(C)(=O)=O)=C1

References

General References
  1. Link [Link]
Human Metabolome Database
HMDB0014421
KEGG Drug
D02321
KEGG Compound
C01553
PubChem Compound
2179
PubChem Substance
46507539
ChemSpider
2094
BindingDB
87351
RxNav
739
ChEBI
2687
ChEMBL
CHEMBL43
ZINC
ZINC000003812923
Therapeutic Targets Database
DAP000046
PharmGKB
PA10309
PDBe Ligand
ASW
Wikipedia
Amsacrine
PDB Entries
4g0u
MSDS
Download (48.7 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Non-Lymphocytic Leukemia1
3CompletedTreatmentLeukemias1
3CompletedTreatmentLeukemias / Myelodysplastic Syndrome1
3CompletedTreatmentLeukemias / Neutropenia1
3RecruitingTreatmentRelapsed or Refractory Acute Myeloid Leukemia (AML)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidIntravenous50 mg / mL
Injection
Injection, powder, for solution75 MG
Injection, solution, concentrateIntravenous75 mg/1.5ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235 °CPhysProp
water solubility<1 mg/mLNot Available
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00317 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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.667
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.766
P-glycoprotein inhibitor INon-inhibitor0.5625
P-glycoprotein inhibitor IINon-inhibitor0.7178
Renal organic cation transporterNon-inhibitor0.8983
CYP450 2C9 substrateNon-substrate0.7427
CYP450 2D6 substrateNon-substrate0.8266
CYP450 3A4 substrateNon-substrate0.5159
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9051
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8098
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2509 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7711
hERG inhibition (predictor II)Inhibitor0.7355
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-MSsplash10-02di-0019000000-7fcad477b7be59278713
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-1009000000-4ba561fecb59da96074a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03xu-0009000000-6c5431bdfc23b950295b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-1009000000-29efd72866e5c9902990
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-2945000000-b849a190b273915ee63b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9007000000-0a86c18b04a882c5a89a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-8592000000-05bc23b80867ec9feb07
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-211.0220399
predicted
DarkChem Lite v0.1.0
[M-H]-196.316
predicted
DeepCCS 1.0 (2019)
[M+H]+212.4600399
predicted
DarkChem Lite v0.1.0
[M+H]+198.674
predicted
DeepCCS 1.0 (2019)
[M+Na]+210.8818399
predicted
DarkChem Lite v0.1.0
[M+Na]+204.76717
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details2. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
Details3. Potassium voltage-gated channel subfamily H member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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 ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
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. [Article]
Details4. Alpha-1-acid glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Finlay GJ, Baguley BC: Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs. Cancer Chemother Pharmacol. 2000;45(5):417-22. [Article]
Details5. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Finlay GJ, Baguley BC: Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs. Cancer Chemother Pharmacol. 2000;45(5):417-22. [Article]

Transporters

Details1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:44