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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
Structure for Amsacrine (DB00276)
- 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
Pharmacology
- Indication
For treatment of acute myeloid leukaemia.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Refractory leukemia •••••••••••• ••••• •••••• •••••••••••• ••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ADNA intercalationHumans ADNA topoisomerase 2-beta inhibitorHumans ADNA topoisomerase 2-alpha inhibitorHumans UVoltage-gated inwardly rectifying potassium channel KCNH2 inhibitorHumans UAlpha-1-acid glycoprotein 1 Not Available Humans UAlbumin Not Available Humans - 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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Symptoms of overdose include nausea and vomiting, diarrhea, some cardiotoxicity (rarely).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Amsacrine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Amsacrine. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Amsacrine. Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Amsacrine. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Amsacrine. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Amsacrine gluconate M4P91439UZ 80277-07-2 XXNAQBNJPZNRSZ-IFWQJVLJSA-N Amsacrine hydrochloride U66HX4K4CO 54301-15-4 WDISRLXRMMTXEV-UHFFFAOYSA-N Amsacrine mesylate 7LWQ0T63UA 54301-16-5 KIDGPIWSXHBPDH-UHFFFAOYSA-N - International/Other Brands
- Amekrin / AMSA P-D / Amsidine / Amsidyl
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Amsa Pd Liquid 50 mg / mL Intravenous Searchlight Pharma Inc 1983-12-31 2024-07-18 Canada 
Categories
- ATC Codes
- L01XX01 — Amsacrine
- Drug Categories
- Acridines
- Aminoacridines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cardiotoxic antineoplastic agents
- Compounds used in a research, industrial, or household setting
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Indicators and Reagents
- Intercalating Agents
- Laboratory Chemicals
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- 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
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Acute Non-Lymphocytic Leukemia 1 somestatus stop reason just information to hide 3 Completed Treatment Leukemias 1 somestatus stop reason just information to hide 3 Completed Treatment Leukemias / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide 3 Completed Treatment Leukemias / Neutropenia 1 somestatus stop reason just information to hide 3 Recruiting Treatment Relapsed or Refractory Acute Myeloid Leukemia (AML) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Liquid Intravenous 50 mg / mL Injection Injection, powder, for solution 75 MG Injection, solution, concentrate Intravenous 75 mg/1.5ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 235 °C PhysProp water solubility <1 mg/mL Not Available logP 3.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00317 mg/mL ALOGPS logP 4.66 ALOGPS logP 3.16 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 10.82 Chemaxon pKa (Strongest Basic) 8.44 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 80.32 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 107.69 m3·mol-1 Chemaxon Polarizability 41.65 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.667 Caco-2 permeable + 0.5 P-glycoprotein substrate Non-substrate 0.766 P-glycoprotein inhibitor I Non-inhibitor 0.5625 P-glycoprotein inhibitor II Non-inhibitor 0.7178 Renal organic cation transporter Non-inhibitor 0.8983 CYP450 2C9 substrate Non-substrate 0.7427 CYP450 2D6 substrate Non-substrate 0.8266 CYP450 3A4 substrate Non-substrate 0.5159 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9232 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9051 Ames test AMES toxic 0.9107 Carcinogenicity Non-carcinogens 0.8098 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.2509 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7711 hERG inhibition (predictor II) Inhibitor 0.7355
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-02di-0019000000-7fcad477b7be59278713 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-1009000000-4ba561fecb59da96074a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03xu-0009000000-6c5431bdfc23b950295b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-1009000000-29efd72866e5c9902990 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-2945000000-b849a190b273915ee63b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9007000000-0a86c18b04a882c5a89a Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-8592000000-05bc23b80867ec9feb07 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 211.0220399 predictedDarkChem Lite v0.1.0 [M-H]- 196.316 predictedDeepCCS 1.0 (2019) [M+H]+ 212.4600399 predictedDarkChem Lite v0.1.0 [M+H]+ 198.674 predictedDeepCCS 1.0 (2019) [M+Na]+ 210.8818399 predictedDarkChem Lite v0.1.0 [M+Na]+ 204.76717 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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Yes
Intercalation
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation
- Specific Function
- ATP binding
- Gene Name
- TOP2B
- Uniprot ID
- Q02880
- Uniprot Name
- DNA topoisomerase 2-beta
- Molecular Weight
- 183265.825 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- TOP2A
- Uniprot ID
- P11388
- Uniprot Name
- DNA topoisomerase 2-alpha
- Molecular Weight
- 174383.88 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
- Specific Function
- delayed rectifier potassium channel activity
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Voltage-gated inwardly rectifying potassium channel KCNH2
- Molecular Weight
- 126653.52 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Functions as a 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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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 August 26, 2024 19:23