AMSACRINE

Possibly Marketed Outside US

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
Target ID: DNA of tumor cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/2602146	Binding Agent 1059
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10691026	Inhibitor 8228

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 8360	AMSA PD Approved Use Unknown

PubMed

Title	Date	PubMed
Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors.	2001 Dec	12041546
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	11860442
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	11710632
Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines.	2001 Oct	11676865
Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study.	2001 Sep	11684850
Inhibition of apoptotic proteins causes multidrug resistance in renal carcinoma cells.	2001 Sep-Oct	11848468
Phase I study of the combination of losoxantrone and cyclophosphamide in patients with refractory solid tumours.	2002 Feb 12	11870533
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
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
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
Point of attachment and sequence of immobilized peptide-acridine conjugates control affinity for nucleic acids.	2002 Jul 24	12121075
A rare case of adenoviral fulminant hepatic necrosis after chemotherapy.	2002 Jul-Aug	12078868
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.	2002 Jun	12082016
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
Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells.	2002 Jun 17	12085191
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
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
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
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
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
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
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
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
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
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
[Disseminated cutaneous and visceral fusariosis in an aplastic patient: an unusual digestive entry].	2005 Mar	15924050
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

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 `Wed Jul 05 22:54:07 UTC 2023` Edited by `admin` on `Wed Jul 05 22:54:07 UTC 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