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
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)
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 |
DescriptionSources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Amsacrine_monograph_1August2013_formatted.pdfCurator'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
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 |
|||
Target ID: CHEMBL1806 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10691026 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | AMSA PD Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Targeting DNA through-covalent interactions of reversible binding drugs. | 2001 |
|
DNA binding properties of the indolocarbazole antitumor drug NB-506. | 2001 Apr-Jun |
|
Effects of anticancer drugs on the metabolism of the anticancer drug 5,6-dimethylxanthenone-4-acetic (DMXAA) by human liver microsomes. | 2001 Aug |
|
Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors. | 2001 Dec |
|
Hypophosphorylation of topoisomerase IIalpha in etoposide (VP-16)-resistant human carcinoma cell lines associated with carboxy-terminal truncation. | 2001 Jul |
|
Expression of drug resistance genes in VP-16 and mAMSA-selected human carcinoma cells. | 2001 Jul |
|
Novel pyrrolo[3,2-f]quinolines: synthesis and antiproliferative activity. | 2001 Jul |
|
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 |
|
Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum). | 2001 Oct 15 |
|
Altered topoisomerase IIalpha and multidrug resistance-associated protein levels during drug selection: adaptations to increasing drug pressure. | 2001 Sep |
|
Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells. | 2001 Sep 1 |
|
Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta. | 2001 Sep 1 |
|
Inhibition of apoptotic proteins causes multidrug resistance in renal carcinoma cells. | 2001 Sep-Oct |
|
Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia. | 2002 Dec |
|
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 |
|
Antitumor activity of ER-37328, a novel carbazole topoisomerase II inhibitor. | 2002 Jan |
|
A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation. | 2002 Jan |
|
Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination. | 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 |
|
A unique type II topoisomerase mutant that is hypersensitive to a broad range of cleavage-inducing antitumor agents. | 2002 Jun 25 |
|
Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1. | 2002 May 6 |
|
Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review. | 2002 Nov-Dec |
|
Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives. | 2002 Oct 10 |
|
Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. | 2002 Sep 1 |
|
[Effect of etoposide and amsacrine on mitotic progression of GM-130 and Hep-2 cell lines. The flow cytometry assay]. | 2003 |
|
Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities. | 2003 Aug |
|
Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk 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 |
|
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 |
|
Free radical scavengers can differentially modulate the genotoxicity of amsacrine in normal and cancer cells. | 2003 Feb 5 |
|
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 |
|
Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for changes in NaeI structure. | 2003 Mar 14 |
|
[Topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies]. | 2003 Nov |
|
Investigations into the biological relevance of in vitro clastogenic and aneugenic activity. | 2004 |
|
Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia. | 2004 Aug |
|
Comparison of BAVC to BuCy regimens in autologous stem cell transplantation for adult patients with acute myeloid leukemia. | 2004 Jan |
|
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 |
|
Dissecting the cell-killing mechanism of the topoisomerase II-targeting drug ICRF-193. | 2004 Jul 2 |
|
Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. | 2004 Jun |
|
Risk-adapted induction and consolidation therapy in adults with de novo AML aged = 60 years: results of a prospective multicenter trial. | 2004 Jun |
|
The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. | 2004 Oct |
|
Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia. | 2004 Oct 15 |
|
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 |
|
Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation. | 2004 Sep 20 |
|
Induction chemotherapy for acute myelogenous leukemia. | 2005 Jan |
|
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 |
|
Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity. | 2005 Jun 2 |
|
E1A specifically enhances sensitivity to topoisomerase IIalpha targeting anticancer drug by up-regulating the promoter activity. | 2005 May |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24122234
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
Edited
Sat Jun 26 00:19:44 UTC 2021
by
admin
on
Sat Jun 26 00:19:44 UTC 2021
|
Record UNII |
00DPD30SOY
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Systematic Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-VATC |
QL01XX01
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
||
|
FDA ORPHAN DRUG |
4584
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
||
|
NCI_THESAURUS |
C582
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
||
|
WHO-ATC |
L01XX01
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
CHEMBL43
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
C240
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
2179
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
51264-14-3
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
7087
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
D000677
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
739
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | RxNorm | ||
|
51264-14-3
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
AMSACRINE
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
DB00276
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
4864
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
M1859
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | Merck Index | ||
|
257-094-3
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
203
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
SUB05495MIG
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY | |||
|
00DPD30SOY
Created by
admin on Sat Jun 26 00:19:44 UTC 2021 , Edited by admin on Sat Jun 26 00:19:44 UTC 2021
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SALT/SOLVATE -> PARENT | |||
|
SALT/SOLVATE -> PARENT | |||
|
BINDER->LIGAND |
BINDING
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Volume of Distribution | PHARMACOKINETIC |
|
|
|||
Biological Half-life | PHARMACOKINETIC |
|
|
|||