AMSACRINE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H19N3O3S
Molecular Weight	393.4607
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COc1cc(ccc1N=c2c3ccccc3[nH]c4ccccc42)NS(=O)(=O)C

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	393.4607
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
Target ID: DNA of tumor cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/2602146	Binding Agent 996
DNA topoisomerase II alpha 34 Target ID: CHEMBL1806 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10691026	Inhibitor 7728

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 8043	AMSA PD Approved Use Unknown

PubMed

Title	Date	PubMed
Targeting DNA through-covalent interactions of reversible binding drugs.	2001	11494860
DNA binding properties of the indolocarbazole antitumor drug NB-506.	2001 Apr-Jun	11962518
Effects of anticancer drugs on the metabolism of the anticancer drug 5,6-dimethylxanthenone-4-acetic (DMXAA) by human liver microsomes.	2001 Aug	11488768
Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors.	2001 Dec	12041546
Hypophosphorylation of topoisomerase IIalpha in etoposide (VP-16)-resistant human carcinoma cell lines associated with carboxy-terminal truncation.	2001 Jul	11473732
Expression of drug resistance genes in VP-16 and mAMSA-selected human carcinoma cells.	2001 Jul	11473729
Novel pyrrolo[3,2-f]quinolines: synthesis and antiproliferative activity.	2001 Jul	11425586
Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution.	2001 May	11438819
Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum).	2001 Oct 15	11597574
Altered topoisomerase IIalpha and multidrug resistance-associated protein levels during drug selection: adaptations to increasing drug pressure.	2001 Sep	11572765
Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells.	2001 Sep 1	11585056
Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta.	2001 Sep 1	11531262
Inhibition of apoptotic proteins causes multidrug resistance in renal carcinoma cells.	2001 Sep-Oct	11848468
Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia.	2002 Dec	12476293
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	11992630
Antitumor activity of ER-37328, a novel carbazole topoisomerase II inhibitor.	2002 Jan	12467211
A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.	2002 Jan	11855748
Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination.	2002 Jan 1	11774253
Tetrakis-acridinyl peptide: a novel fluorometric reagent for nucleic acid analysis based on the fluorescence dequenching upon DNA binding.	2002 Jul	12173644
Point of attachment and sequence of immobilized peptide-acridine conjugates control affinity for nucleic acids.	2002 Jul 24	12121075
A unique type II topoisomerase mutant that is hypersensitive to a broad range of cleavage-inducing antitumor agents.	2002 Jun 25	12069589
Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1.	2002 May 6	11986786
Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review.	2002 Nov-Dec	12432417
Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives.	2002 Oct 10	12361395
Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I.	2002 Sep 1	12027807
[Effect of etoposide and amsacrine on mitotic progression of GM-130 and Hep-2 cell lines. The flow cytometry assay].	2003	12683237
Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities.	2003 Aug	12960734
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
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	12393725
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
Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for changes in NaeI structure.	2003 Mar 14	12519752
[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
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
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
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
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
Induction chemotherapy for acute myelogenous leukemia.	2005 Jan	15610659
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
Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity.	2005 Jun 2	15911312
E1A specifically enhances sensitivity to topoisomerase IIalpha targeting anticancer drug by up-regulating the promoter activity.	2005 May	15886298

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 `Sat Jun 26 00:19:44 UTC 2021` Edited by `admin` on `Sat Jun 26 00:19:44 UTC 2021`
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

AMSACRINE [WHO-DD]

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

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