Details
Stereochemistry | RACEMIC |
Molecular Formula | C21H19N3O3S.C3H6O3 |
Molecular Weight | 483.537 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)C(O)=O.COC1=C(NC2=C3C=CC=CC3=NC4=C2C=CC=C4)C=CC(NS(C)(=O)=O)=C1
InChI
InChIKey=NYGZSXVEKMITFN-UHFFFAOYSA-N
InChI=1S/C21H19N3O3S.C3H6O3/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;1-2(4)3(5)6/h3-13,24H,1-2H3,(H,22,23);2,4H,1H3,(H,5,6)
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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Mutations at arg486 and glu571 in human topoisomerase IIalpha confer resistance to amsacrine: relevance for antitumor drug resistance in human cells. | 2000 Apr |
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Selection of an unnatural peptide library for dsDNA binding. | 2001 Apr |
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Reciprocal control of expression of mRNAs for osteoclast differentiation factor and OPG in osteogenic stromal cells by genistein: evidence for the involvement of topoisomerase II in osteoclastogenesis. | 2001 Aug |
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Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon. | 2001 Feb |
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Atypical multidrug resistance may be associated with catalytically active mutants of human DNA topoisomerase II alpha. | 2001 Jul 11 |
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Pretreatment leukaemia cell drug resistance is correlated to clinical outcome in acute myeloid leukaemia. | 2001 Mar |
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Paclitaxel sensitization of multidrug-resistant cells to chemotherapy is independent of the cell cycle. | 2001 Mar 1 |
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Repair of topoisomerase-mediated DNA damage in bacteriophage T4. | 2001 May |
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Atp-bound topoisomerase ii as a target for antitumor drugs. | 2001 May 11 |
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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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Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum). | 2001 Oct 15 |
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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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Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta. | 2001 Sep 1 |
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Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia. | 2002 Dec |
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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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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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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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Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review. | 2002 Nov-Dec |
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Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. | 2002 Sep 1 |
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Phosphorylation of serine 1106 in the catalytic domain of topoisomerase II alpha regulates enzymatic activity and drug sensitivity. | 2003 Apr 11 |
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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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Mechanisms of action of DNA intercalating acridine-based drugs: how important are contributions from electron transfer and oxidative stress? | 2003 Dec |
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Free radical scavengers can differentially modulate the genotoxicity of amsacrine in normal and cancer cells. | 2003 Feb 5 |
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Salvage therapy in refractory acute myeloid leukemia: prediction of outcome based on analysis of prognostic factors. | 2003 Mar |
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Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for changes in NaeI structure. | 2003 Mar 14 |
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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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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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Comparison of BAVC to BuCy regimens in autologous stem cell transplantation for adult patients with acute myeloid leukemia. | 2004 Jan |
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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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A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. | 2004 Jun 15 |
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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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Establishment and characterisation of a human carcinoma cell line with acquired resistance to Aplidin. | 2004 Oct 4 |
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Cardiotoxicity of cancer chemotherapy: implications for children. | 2005 |
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Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation. | 2005 Jun |
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Synthesis and antitumor activity of sulfur-containing 9-anilinoacridines. | 2005 Mar-Apr |
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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 |
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Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes. | 2006 Jan |
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.
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C582
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C96771
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80277-11-8
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD