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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
Structure of AMSACRINE LACTATE

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)

HIDE SMILES / InChI

Molecular Formula C3H6O3
Molecular Weight 90.0779
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AMSA PD

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Mutations at arg486 and glu571 in human topoisomerase IIalpha confer resistance to amsacrine: relevance for antitumor drug resistance in human cells.
2000 Apr
Selection of an unnatural peptide library for dsDNA binding.
2001 Apr
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
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
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
Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines.
2001 Oct
Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum).
2001 Oct 15
Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study.
2001 Sep
Phase I study of the combination of losoxantrone and cyclophosphamide in patients with refractory solid tumours.
2002 Feb 12
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
Tetrakis-acridinyl peptide: a novel fluorometric reagent for nucleic acid analysis based on the fluorescence dequenching upon DNA binding.
2002 Jul
Point of attachment and sequence of immobilized peptide-acridine conjugates control affinity for nucleic acids.
2002 Jul 24
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.
2002 Jun
Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I.
2002 Sep 1
Acute pericarditis and pleural effusion complicating cytarabine chemotherapy.
2003 Aug
Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities.
2003 Aug
Increased in vitro cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia.
2003 Aug
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
Mechanisms of action of DNA intercalating acridine-based drugs: how important are contributions from electron transfer and oxidative stress?
2003 Dec
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
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
Salvage therapy in refractory acute myeloid leukemia: prediction of outcome based on analysis of prognostic factors.
2003 Mar
In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia.
2003 May
Dinucleoside monophosphates containing AZT and 1-methyladenosine or 7-methylguanosine.
2003 May-Aug
Investigations into the biological relevance of in vitro clastogenic and aneugenic activity.
2004
Maintenance therapy in childhood acute myeloid leukemia.
2004
Rescue therapy combining intermediate-dose cytarabine with amsacrine and etoposide in relapsed adult acute lymphoblastic leukemia.
2004
Topoisomerase I and II inhibitors control caspase-2 pre-messenger RNA splicing in human cells.
2004 Jan
Dissecting the cell-killing mechanism of the topoisomerase II-targeting drug ICRF-193.
2004 Jul 2
Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia.
2004 Oct 15
Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation.
2004 Sep 20
Cardiotoxicity of cancer chemotherapy: implications for children.
2005
Synthesis, antitumour activity and structure-activity relationships of 5H-benzo[b]carbazoles.
2005 Feb 1
Random mutagenesis of the B'A' core domain of yeast DNA topoisomerase II and large-scale screens of mutants resistant to the anticancer drug etoposide.
2005 Feb 11
BAVC regimen and autologous bone marrow transplantation for APL patients in second molecular remission: updated results.
2005 Jul
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
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
Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity.
2005 Jun 2
[Disseminated cutaneous and visceral fusariosis in an aplastic patient: an unusual digestive entry].
2005 Mar
Synthesis and antitumor activity of sulfur-containing 9-anilinoacridines.
2005 Mar-Apr
E1A specifically enhances sensitivity to topoisomerase IIalpha targeting anticancer drug by up-regulating the promoter activity.
2005 May
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
Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes.
2006 Jan
Patents

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
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
by admin
on Fri Dec 15 18:31:51 UTC 2023
Edited
by admin
on Fri Dec 15 18:31:51 UTC 2023
Record UNII
959PWE0Q2E
Record Status Validated (UNII)
Record Version
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Name Type Language
AMSACRINE LACTATE
Common Name English
PROPANOIC ACID, 2-HYDROXY-, COMPD. WITH N-(4-(9-ACRIDINYLAMINO)-3-METHOXYPHENYL)METHANESULFONAMIDE (1:1)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C582
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID701001137
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
PRIMARY
FDA UNII
959PWE0Q2E
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
PRIMARY
NCI_THESAURUS
C96771
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
PRIMARY
PUBCHEM
88124
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
PRIMARY
CAS
80277-11-8
Created by admin on Fri Dec 15 18:31:51 UTC 2023 , Edited by admin on Fri Dec 15 18:31:51 UTC 2023
PRIMARY
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ACTIVE MOIETY