AMSACRINE

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

Structure Search

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)

HIDE SMILES / InChI

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
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
DNA of tumor cells 4 Target ID: DNA of tumor cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/2602146	Binding Agent 1064
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10691026	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Leukemia, acute 4 Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Amsacrine_monograph_1August2013_formatted.pdf	Primary		Approved 8429	AMSA PD Approved Use Unknown

PubMed

Title	Date	PubMed
Design of new anti-cancer agents based on topoisomerase poisons targeted to specific DNA sequences.	2001 Nov	12678755
Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia.	2002 Dec	12476293
[Effect of etoposide and amsacrine on mitotic progression of GM-130 and Hep-2 cell lines. The flow cytometry assay].	2003	12683237
Phosphorylation of serine 1106 in the catalytic domain of topoisomerase II alpha regulates enzymatic activity and drug sensitivity.	2003 Apr 11	12569090
Acute pericarditis and pleural effusion complicating cytarabine chemotherapy.	2003 Aug	12972701
Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities.	2003 Aug	12960734
Increased in vitro cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia.	2003 Aug	12877664
Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia.	2003 Aug	12858198
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	14647265
Mechanisms of action of DNA intercalating acridine-based drugs: how important are contributions from electron transfer and oxidative stress?	2003 Dec	14529454
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	12933575
Free radical scavengers can differentially modulate the genotoxicity of amsacrine in normal and cancer cells.	2003 Feb 5	12547280
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	12527422
A preliminary evaluation of a new selective agar supplemented with desferrioxamine for detection of methicillin-resistant Staphylococcus aureus.	2003 Jul	12855238
Salvage therapy in refractory acute myeloid leukemia: prediction of outcome based on analysis of prognostic factors.	2003 Mar	12537972
Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for changes in NaeI structure.	2003 Mar 14	12519752
In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia.	2003 May	12802914
Dinucleoside monophosphates containing AZT and 1-methyladenosine or 7-methylguanosine.	2003 May-Aug	14565295
[Topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies].	2003 Nov	14690573
Investigations into the biological relevance of in vitro clastogenic and aneugenic activity.	2004	15162052
Maintenance therapy in childhood acute myeloid leukemia.	2004	15124700
Rescue therapy combining intermediate-dose cytarabine with amsacrine and etoposide in relapsed adult acute lymphoblastic leukemia.	2004	15048062
Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia.	2004 Aug	15156346
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	15575955
Differences in the longevity of topo IIalpha and topo IIbeta drug-stabilized cleavable complexes and the relationship to drug sensitivity.	2004 Feb	14504921
Topoisomerase I and II inhibitors control caspase-2 pre-messenger RNA splicing in human cells.	2004 Jan	14757846
Comparison of BAVC to BuCy regimens in autologous stem cell transplantation for adult patients with acute myeloid leukemia.	2004 Jan	14754615
Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout cells to antitumor triazoloacridone C-1305 is associated with permanent G2 cell cycle arrest.	2004 Jul 1	15231658
Dissecting the cell-killing mechanism of the topoisomerase II-targeting drug ICRF-193.	2004 Jul 2	15123716
Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action.	2004 Jun	15148258
Risk-adapted induction and consolidation therapy in adults with de novo AML aged	2004 Jun	15034758
A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia.	2004 Jun 15	15010369
The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties.	2004 Oct	15258255
Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia.	2004 Oct 15	15217836
Establishment and characterisation of a human carcinoma cell line with acquired resistance to Aplidin.	2004 Oct 4	15365569
Mutation E522K in human DNA topoisomerase IIbeta confers resistance to methyl N-(4'-(9-acridinylamino)-phenyl)carbamate hydrochloride and methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide but hypersensitivity to etoposide.	2004 Sep	15322234
Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation.	2004 Sep 20	15324894
Cardiotoxicity of cancer chemotherapy: implications for children.	2005	15977964
Synthesis, antitumour activity and structure-activity relationships of 5H-benzo[b]carbazoles.	2005 Feb 1	15653349
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	15629155
Induction chemotherapy for acute myelogenous leukemia.	2005 Jan	15610659
BAVC regimen and autologous bone marrow transplantation for APL patients in second molecular remission: updated results.	2005 Jul	15880128
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	15925259
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	16019530
Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity.	2005 Jun 2	15911312
[Disseminated cutaneous and visceral fusariosis in an aplastic patient: an unusual digestive entry].	2005 Mar	15924050
Synthesis and antitumor activity of sulfur-containing 9-anilinoacridines.	2005 Mar-Apr	15804186
E1A specifically enhances sensitivity to topoisomerase IIalpha targeting anticancer drug by up-regulating the promoter activity.	2005 May	15886298
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	16038735
Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes.	2006 Jan	16052237

Patents

Sample Use Guides

In Vivo Use Guide

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

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 15:23:44 GMT 2023` Edited by `admin` on `Fri Dec 15 15:23:44 GMT 2023`
Record UNII	00DPD30SOY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMSACRINE

Official Name

English

N-(4-(9-ACRIDINYLAMINO)-3-METHOXYPHENYL)METHANESULFONAMIDE

Systematic Name

English

METHANESULFONAMIDE, N-(4-(9-ACRIDINYLAMINO)-3-METHOXYPHENYL)-

Systematic Name

English

amsacrine [INN]

Common Name

English

AMSACRINE [IARC]

Common Name

English

AMSACRINE [VANDF]

Common Name

English

AMSACRINE [HSDB]

Common Name

English

AMSIDINE

Brand Name

English

ACRIDINYLANISIDIDE

Common Name

English

AMSIDYL

Brand Name

English

M-AMSA

Code

English

SN-11841

Code

English

AMSACRINE [MART.]

Common Name

English

NCI-249992

Code

English

SN-21429

Code

English

AMSACRINE [USAN]

Common Name

English

CI-880

Code

English

Amsacrine [WHO-DD]

Common Name

English

AMEKRIN

Brand Name

English

NSC-156303

Code

English

AMSACRINE [MI]

Common Name

English

NSC-249992

Code

English

LAMASINE

Brand Name

English

AMSIDIL

Brand Name

English

4'-(9-ACRIDINYLAMINO)METHANESULFON-M-ANISIDIDE

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QL01XX01