Page last updated: 2024-12-06

intoplicine

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

Description

Intoplicine is a naturally occurring indole alkaloid isolated from the stem bark of the African medicinal plant _Rauvolfia vomitoria_. It exhibits a variety of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory, and anti-malarial properties. Intoplicine has been shown to inhibit the growth of several cancer cell lines _in vitro_ and has been investigated as a potential treatment for leukemia, breast cancer, and other malignancies. Its mechanism of action involves the inhibition of topoisomerase I, an enzyme essential for DNA replication. Research efforts focus on understanding the molecular basis of its anticancer activity, developing more potent analogs, and evaluating its potential clinical applications.'

intoplicine: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID65954
CHEMBL ID1908351
CHEBI ID135474
SCHEMBL ID420414
MeSH IDM0218207

Synonyms (28)

Synonym
NCI60_015286
NEURO_000335
rp 60475
intoplicine
rp-60475
11-[[3-(dimethylamino)propyl]amino]-8-methyl-7h-benzo[e]pyrido[4,3-b]indol-3-ol
125974-72-3
[3-(dimethylamino)propylamino]-methyl-[?]ol
CHEBI:135474
7h-benzo(e)pyrido(4,3-b)indol-3-ol, 11-((3-(dimethylamino)propyl)amino)-8-methyl-
intoplicine [inn]
unii-fb2cin6hmi
fb2cin6hmi ,
11-((3-(dimethylamino)propyl)amino)-8-methyl-7h-benzo(e)pyrido(4,3-b)indol-3-ol
rp-60475 free base
CHEMBL1908351
SCHEMBL420414
intoplicine [who-dd]
DTXSID80155022
HY-101647
CS-6640
16-[3-(dimethylamino)propylamino]-13-methyl-11,15-diazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),3,5,8,12(17),13,15-octaen-5-ol
DB12868
ethyl2-isocyanatopropionate
Q27277895
11-((3-(dimethylamino)propyl)amino)-8-methyl-7h-benzo[e]pyrido[4,3-b]indol-3-ol
MS-25375
AKOS040741882

Research Excerpts

Overview

Intoplicine is a 7H-benzo[e]pyrido[4,3-b]indole. It inhibits DNA nicking and closing reactions by stabilizing the cleavable complex.

ExcerptReferenceRelevance
"Intoplicine was found to be a dual topoisomerase I and II inhibitor, with DNA sites of enzyme inhibition being different for these two enzymes."( Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities.
Bisagni, E; Bissery, MC; Fossé, P; Grondard, L; Larsen, AK; Lavelle, F; Nguyen, CH; Riou, JF; Saucier, JM, 1993
)
2.45
"Intoplicine is a 7H-benzo[e]pyrido[4,3-b]indole that inhibits DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA."( Phase I trial of intoplicine (RP 60475) administered as a 72 h infusion every 3 weeks in patients with solid tumors.
Bayssas, M; Bruno, R; Kim, J; Klink-Alaki, M; Newman, BM; Newman, RA; Pazdur, R, 1999
)
1.36

Pharmacokinetics

ExcerptReferenceRelevance
" 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
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
pyridoindole
[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
AID226371Tested for medium tumor weight of treated /control animals x 100 (% T/C) for murine solid tumor model 3LL early stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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.
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID226549Tested for medium tumor weight of treated /control animals x 100 (% T/C) for murine solid tumor model C26 early stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID84434Antiproliferative activity against human HT-29 colon cell line1999Bioorganic & medicinal chemistry letters, Sep-06, Volume: 9, Issue:17
BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II.
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]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID226547Tested for medium tumor weight of treated /control animals x 100 (% T/C) for murine solid tumor model B16 early stage that is subcutaneously implanted by the intravenous treatment at the dose of 5 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1580230Antitumor activity against mouse P388 cells implanted in ip dosed B6D2F1 mouse assessed as T/C value administered for 4 days2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Dual Inhibitors of Human DNA Topoisomerase II and Other Cancer-Related Targets.
AID55802Antiproliferative activity against human DU145 prostate cell line1999Bioorganic & medicinal chemistry letters, Sep-06, Volume: 9, Issue:17
BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II.
AID224102In vivo total number of survivors was determined against L1210 Leukemia cells out of 8 mouse at 50 day1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID226552Tested for the change in body weight between day1 and 7 for murine solid tumor model MA 16/C early stage that is subcutaneously implanted by the intravenous treatment1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID101509Cytotoxicity in the multiple tumor disk diffusion soft agar assay at the dose of 15 ug/disk against leukemia L12101990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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]
AID226370Tested for the change in body weight between day 1 and 7 for murine solid tumor model 3LL advanced stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID154582In vivo T/C (survival time treated/survival time control x 100) was determined against P388 leukemia cells at 10 mg/Kg1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID226546Tested for the change in body weight between day 1 and 7 for murine solid tumor model 3LL early stage that is subcutaneously implanted by the intravenous treatment at the dose of 5 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID153673In vitro cytotoxicity was determined against P388 leukemia cells1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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]
AID205459Tested for cytotoxicity in the multiple tumor disk diffusion soft agar assay at the dose of 15 ug/disk against solid tumor C381990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID99295In vivo T/C (survival time treated/survival time control x 100) was determined against L1210 leukemia cells at 10 mg/Kg1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID154586In vivo T/C (survival time treated/survival time control x 100) was determined against P388 leukemia cells at 5.0 mg/Kg1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID103441Antiproliferative activity against human MCF-7 breast cell line1999Bioorganic & medicinal chemistry letters, Sep-06, Volume: 9, Issue:17
BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II.
AID226548Tested for the change in body weight between day 1 and 7 for murine solid tumor model B16 early stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID226369Tested for medium tumor weight of treated /control animals x 100 (% T/C) for murine solid tumor model 3LL advanced stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
AID226550Tested for the change in body weight between day 1 and 7 for murine solid tumor model C26 early stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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.
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]
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]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID202842Antiproliferative activity against human SKOV-3 ovarian cell line1999Bioorganic & medicinal chemistry letters, Sep-06, Volume: 9, Issue:17
BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID226551Tested for medium tumor weight of treated /control animals x 100 (% T/C) for murine solid tumor model MA 16/C early stage that is subcutaneously implanted by the intravenous treatment at the dose of 10 mg/kg in 1-4 schedule1990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
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.
AID205460Cytotoxicity in the multiple tumor disk diffusion soft agar assay at the dose of 15 ug/disk against solid tumor PO31990Journal of medicinal chemistry, May, Volume: 33, Issue:5
Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (20)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's16 (80.00)18.2507
2000's2 (10.00)29.6817
2010's1 (5.00)24.3611
2020's1 (5.00)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 (%)
Trials5 (21.74%)5.53%
Reviews2 (8.70%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other16 (69.57%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]