Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H19N3O3S |
Molecular Weight | 393.459 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(NC2=C3C=CC=CC3=NC4=C2C=CC=C4)C=CC(NS(C)(=O)=O)=C1
InChI
InChIKey=XCPGHVQEEXUHNC-UHFFFAOYSA-N
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)
Molecular Formula | C21H19N3O3S |
Molecular Weight | 393.459 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Amsacrine_monograph_1August2013_formatted.pdfCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/2602146
https://www.ncbi.nlm.nih.gov/pubmed/16330449
Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Amsacrine_monograph_1August2013_formatted.pdf
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/2602146
https://www.ncbi.nlm.nih.gov/pubmed/16330449
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. Although its mechanism of action is incompletely defined, amsacrine inhibits DNA synthesis by binding to and intercalating with DNA. Amsacrine also inhibits topoisomerase II activity and may exert an effect on cell membranes. This agent also possesses immunosuppressive and antiviral properties. While amsacrine is not cell cycle phase-specific, cytotoxicity is maximal during the G2 and S phases.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: DNA of tumor cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/2602146 |
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Target ID: CHEMBL1806 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10691026 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | AMSA PD Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors. | 2001 Dec |
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FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia. | 2001 Oct |
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Co-amplification of dhfr and a homologue of hmsh3 in a Chinese hamster methotrexate-resistant cell line correlates with resistance to a range of chemotherapeutic drugs. | 2001 Oct |
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Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines. | 2001 Oct |
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Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study. | 2001 Sep |
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Inhibition of apoptotic proteins causes multidrug resistance in renal carcinoma cells. | 2001 Sep-Oct |
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Phase I study of the combination of losoxantrone and cyclophosphamide in patients with refractory solid tumours. | 2002 Feb 12 |
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The modulation of the DNA-damaging effect of polycyclic aromatic agents by xanthines. Part I. Reduction of cytostatic effects of quinacrine mustard by caffeine. | 2002 Feb 15 |
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A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation. | 2002 Jan |
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Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination. | 2002 Jan 1 |
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Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. | 2002 Jan 1 |
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Point of attachment and sequence of immobilized peptide-acridine conjugates control affinity for nucleic acids. | 2002 Jul 24 |
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A rare case of adenoviral fulminant hepatic necrosis after chemotherapy. | 2002 Jul-Aug |
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High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. | 2002 Jun |
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Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant. | 2002 Jun 15 |
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Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells. | 2002 Jun 17 |
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A unique type II topoisomerase mutant that is hypersensitive to a broad range of cleavage-inducing antitumor agents. | 2002 Jun 25 |
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Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1. | 2002 May 6 |
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Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review. | 2002 Nov-Dec |
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Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives. | 2002 Oct 10 |
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Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. | 2002 Sep 1 |
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[Effect of etoposide and amsacrine on mitotic progression of GM-130 and Hep-2 cell lines. The flow cytometry assay]. | 2003 |
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Acute pericarditis and pleural effusion complicating cytarabine chemotherapy. | 2003 Aug |
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Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities. | 2003 Aug |
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More efficient mobilisation of peripheral blood stem cells with HiDAC+AMSA+G-CSF than with mini-ICE+G-CSF in patients with AML. | 2003 Dec |
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A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. | 2003 Dec 15 |
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Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission. | 2003 Feb 15 |
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Crystallization and preliminary X-ray analysis of anti-cancer agent 3-(9-acridinylamino)-5-(hydroxymethyl)aniline complexed with the DNA hexamer d(CGTACG)2. | 2003 Jan 3 |
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In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia. | 2003 May |
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Dinucleoside monophosphates containing AZT and 1-methyladenosine or 7-methylguanosine. | 2003 May-Aug |
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[Topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies]. | 2003 Nov |
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Investigations into the biological relevance of in vitro clastogenic and aneugenic activity. | 2004 |
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Maintenance therapy in childhood acute myeloid leukemia. | 2004 |
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Rescue therapy combining intermediate-dose cytarabine with amsacrine and etoposide in relapsed adult acute lymphoblastic leukemia. | 2004 |
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Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia. | 2004 Aug |
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Characterisation of cytotoxicity and DNA damage induced by the topoisomerase II-directed bisdioxopiperazine anti-cancer agent ICRF-187 (dexrazoxane) in yeast and mammalian cells. | 2004 Dec 2 |
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Differences in the longevity of topo IIalpha and topo IIbeta drug-stabilized cleavable complexes and the relationship to drug sensitivity. | 2004 Feb |
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Topoisomerase I and II inhibitors control caspase-2 pre-messenger RNA splicing in human cells. | 2004 Jan |
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Dissecting the cell-killing mechanism of the topoisomerase II-targeting drug ICRF-193. | 2004 Jul 2 |
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Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. | 2004 Jun |
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Risk-adapted induction and consolidation therapy in adults with de novo AML aged = 60 years: results of a prospective multicenter trial. | 2004 Jun |
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The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. | 2004 Oct |
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Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia. | 2004 Oct 15 |
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Cardiotoxicity of cancer chemotherapy: implications for children. | 2005 |
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Synthesis, antitumour activity and structure-activity relationships of 5H-benzo[b]carbazoles. | 2005 Feb 1 |
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Highly sensitive analysis of the anti-tumor agent 1-[4-(furo[2,3-b]-quinolin-4-ylamino)phenyl]ethanone in rat plasma by high-performance liquid chromatography using electrochemical detection. | 2005 Jul 1 |
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Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity. | 2005 Jun 2 |
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[Disseminated cutaneous and visceral fusariosis in an aplastic patient: an unusual digestive entry]. | 2005 Mar |
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E1A specifically enhances sensitivity to topoisomerase IIalpha targeting anticancer drug by up-regulating the promoter activity. | 2005 May |
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In vitro activity of the flt3-inhibitor su5614 and standard cytotoxic agents in tumour cells from patients with wild type and mutated flt3 acute myeloid leukaemia. | 2005 Sep |
Sample Use Guides
Adults: Cycle Length 3-4 weeks, induction: 75-125 mg/m2 IV once daily for 5 consecutive days starting on day 1 (total dose per cycle 375-625 mg/m2) dose should be increased by 20% in the second and each subsequent cycle if marrow hypoplasia has not been achieved and the patient has had no significant toxicity in the preceding cycle.
4-8 weeks, maintenance: approximately half of the induction dose dependant on blood counts
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24122234
Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells.
Substance Class |
Chemical
Created
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Record UNII |
00DPD30SOY
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Validated (UNII)
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WHO-VATC |
QL01XX01
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FDA ORPHAN DRUG |
4584
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C582
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WHO-ATC |
L01XX01
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156303
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CHEMBL43
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C240
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100000091914
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DTXSID4022604
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AMSACRINE
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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