Page last updated: 2024-12-07

asulacrine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

asulacrine: derivative of amsacrine; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID107924
CHEMBL ID48880
CHEBI ID135753
SCHEMBL ID18672
MeSH IDM0538155

Synonyms (18)

Synonym
ci-921
nsc 343499
4-acridinecarboxamide, 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-n,5-dimethyl-
asulacrine [ban]
ccris 1030
ci 921
asulacrine
9-(2-methoxy-4-(methylsulfonylamino)anilino)-n,5-dimethylacridine-4-carboxamide
CHEBI:135753
80841-47-0
sn-21407
CHEMBL48880
unii-s8p50t62b6
s8p50t62b6 ,
SCHEMBL18672
DTXSID00230663
Q27289054
asulacrine free base

Research Excerpts

Overview

Asulacrine (ASL) is an inhibitor of topoisomerase II, which has shown potential against breast and lung cancer. A high incidence of phlebitis hampered its further development.

ExcerptReferenceRelevance
"Asulacrine (ASL) is a broad-spectrum, antitumor drug whose data are promising for the treatment of breast and lung cancers; however, a high incidence of phlebitis hampered its further development. "( Identification and characterization of in vivo metabolites of asulacrine using advanced mass spectrophotometry technique in combination with improved data mining strategy.
Afzal, A; Peng, Y; Sarfraz, M; Sheng, L; Sun, J; Wang, G; Wu, Z; Zhong, Y, 2016
)
2.12
"Asulacrine (ASL) is an inhibitor of topoisomerase II, which has shown potential against breast and lung cancer. "( Formulation and pharmacokinetic evaluation of an asulacrine nanocrystalline suspension for intravenous delivery.
Baguley, BC; Ganta, S; Garg, S; Paxton, JW, 2009
)
2.05

Pharmacokinetics

ExcerptReferenceRelevance
"The aim was to investigate interspecies relationships between body weight (W) (kg) and various pharmacokinetic parameters for the anti-tumor agents amsacrine and its 4-methyl-5-(N-methylcarboxamide) analogue, CI-921, and examine which pharmacokinetic parameter, if any, might be used to predict the toxicity of these agents."( Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI-921, a new analogue, in mice, rats, rabbits, dogs, and humans.
Kim, SN; Paxton, JW; Whitfield, LR, 1990
)
0.28
" There was no significant difference between distribution and elimination half-life and mean residence time, but the apparent volume of distribution (means, 121 vs 45 l/kg) and clearance (means, 46."( Comparison of the pharmacokinetics and protein binding of the anticancer drug, amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino)phenyl-amino] -4-acridinecarboxamide in rabbits.
Jurlina, JL; Paxton, JW, 1986
)
0.27
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
"04lh(-1)kg(-1)) and elimination half-life (6."( Formulation and pharmacokinetic evaluation of an asulacrine nanocrystalline suspension for intravenous delivery.
Baguley, BC; Ganta, S; Garg, S; Paxton, JW, 2009
)
0.61

Bioavailability

ExcerptReferenceRelevance
" The mean bioavailability for amsacrine was 50% +/- 17 (s."( The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-4 acridinecarboxamide in rabbits.
Paxton, JW, 1986
)
0.27
" Preclinical studies demonstrated that amsalog is active orally: a clinical study of the oral bioavailability of amsalog was therefore performed."( A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.
Carmichael, J; Clayton, K; Fyfe, D; Gardner, C; Halbert, G; Judson, I; Langley, RE; Newell, DR; Raynaud, F; Woll, PJ, 2002
)
0.31
" Doses were escalated further in subsequent cohorts, based on oral bioavailability and toxicity."( A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.
Carmichael, J; Clayton, K; Fyfe, D; Gardner, C; Halbert, G; Judson, I; Langley, RE; Newell, DR; Raynaud, F; Woll, PJ, 2002
)
0.31
"Oral bioavailability of 50 mg/m2 amsalog was 34%."( A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.
Carmichael, J; Clayton, K; Fyfe, D; Gardner, C; Halbert, G; Judson, I; Langley, RE; Newell, DR; Raynaud, F; Woll, PJ, 2002
)
0.31

Dosage Studied

ExcerptRelevanceReference
" This study suggests that oral dosing may be a possible alternative route for the administration of these anticancer agents."( The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-4 acridinecarboxamide in rabbits.
Paxton, JW, 1986
)
0.27
" Although intraperitoneal dosage was superior to intravenous or oral dosage for the treatment of intraperitoneally inoculated P388 leukaemia, all three routes of administration provided similar results with intravenously inoculated Lewis lung or subcutaneously implanted P388 cells."( Schedule dependence of activity of the amsacrine analogue CI-921 towards P388 leukaemia and Lewis lung carcinoma.
Baguley, BC; Grimwade, CD; Kernohan, AR, 1985
)
0.27
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
acridines
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (49)

Assay IDTitleYearJournalArticle
AID55121Binding constant (log K) for DNA binding by ethidium bromide displacement1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID78828In vitro for the inhibition of human colon tumor (HCT-8) cells.1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID152884In vivo for antitumor activity against P388 leukemia1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID103448In vivo antitumor activity against Lewis lung carcinoma cells1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID103617In vivo for antitumor activity against Lewis lung carcinoma1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID153024In vivo for antitumor activity against P388 leukemia.1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID55122Binding constant (log K) for DNA by ethidium bromide displacement1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID55136DNA binding affinity as log K value1984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.
AID154025In vivo antitumor activity against P388 cells expressed as percent increase in lifespan at an optimal dose of 20 mg/kg/day ip1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID78992In vitro for cytotoxicity against human colon tumor cells (HCT-8) in culture1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID96799In vitro concentration required to reduce the murine L1210 leukemia cells in cultures to 50% after a period of 72 hr.1984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.
AID153435In vivo antitumor activity in mice bearing P388 leukemia cells at an optimal dose of 20 mg/kg given on days 1,5,91984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID229284Ratio of IC50 of HCT-8 to IC50 of L1210 cell lines1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID153442In vivo antitumor activity in mice bearing P388 leukemia cells at an optimal dose of 50 mg/kg given on days 1,5,91984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID150213In vivo activity against P388 leukemia cells1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID103610In vivo antitumor activity against Lewis lung carcinoma cells expressed as percent increase in lifespan at an optimal dose of 30 mg/kg/day1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID25353Compound was evaluated for its rate of absorption from the intestine and pKa value was determined, lower value indicate high absorption from gastrointestinal tract. 1984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID103470In vivo for antitumor activity against Lewis lung carcinoma1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID29364pKa values were determined spectrophotometrically in 20% DMF.1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID98378In vitro inhibitory activity against Murine leukemia (L1210)1987Journal of medicinal chemistry, Apr, Volume: 30, Issue:4
Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID232616Ratio of IC50 against murine leukemia cells (L1210) to that of IC50 against colon tumor cells (HCT-8)1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID152553In vivo for antitumor activity against P388 leukemia1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID98133In vitro for cytotoxicity against murine leukemia cells (L1210)1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1609092Cytotoxicity against mouse RAW264.7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay2019European journal of medicinal chemistry, Nov-15, Volume: 182Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID103445Evaluated in vivo for antitumor activity against Lewis lung carcinoma1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (53)

TimeframeStudies, This Drug (%)All Drugs %
pre-199027 (50.94)18.7374
1990's11 (20.75)18.2507
2000's5 (9.43)29.6817
2010's10 (18.87)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (5.45%)5.53%
Reviews2 (3.64%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other50 (90.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]