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
Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs.	2000	10803926
Targeting DNA through-covalent interactions of reversible binding drugs.	2001	11494860
Cell-cycle analysis of drug-treated cells.	2001	11089235
Analysis of cleavage complexes using reactive inhibitor derivatives.	2001	11089223
A phase I trial of amsalog (CI-921) administered by intravenous infusion using a 5-day schedule.	2001 Apr	11345650
Pretreatment leukaemia cell drug resistance is correlated to clinical outcome in acute myeloid leukaemia.	2001 Mar	11350484
Repair of topoisomerase-mediated DNA damage in bacteriophage T4.	2001 May	11333215
Atp-bound topoisomerase ii as a target for antitumor drugs.	2001 May 11	11278845
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
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	11756178
A rare case of adenoviral fulminant hepatic necrosis after chemotherapy.	2002 Jul-Aug	12078868
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	12065553
A unique type II topoisomerase mutant that is hypersensitive to a broad range of cleavage-inducing antitumor agents.	2002 Jun 25	12069589
Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives.	2002 Oct 10	12361395
Increased in vitro cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia.	2003 Aug	12877664
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
Rescue therapy combining intermediate-dose cytarabine with amsacrine and etoposide in relapsed adult acute lymphoblastic leukemia.	2004	15048062
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
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
Induction chemotherapy for acute myelogenous leukemia.	2005 Jan	15610659
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