Page last updated: 2024-11-11

fostriecin

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

Description

fostriecin: compound contains a conjugated triene and an unsaturated lactone; from Streptomyces pulveraceus; structure given in second source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

fostriecin : A structurally unique, naturally-occurring phosphate monoester isolated from the soil bacterium Streptomyces pulveraceus. It inhibits DNA topoisomerase II as well as several protein phosphatase including PP2A and PPA4, and exhibits potent antitumor activity against several cancer cell lines. [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]

Cross-References

ID SourceID
PubMed CID6913994
CHEMBL ID17377
SCHEMBL ID10030539
MeSH IDM0120115

Synonyms (41)

Synonym
[(1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-1-[(2r)-6-oxo-2,3-dihydropyran-2-yl]trideca-1,7,9,11-tetraen-4-yl] dihydrogen phosphate
ci-920
cl-1565a
fostriecin
NSC339638 ,
phosphotrienin
nsc-339638
87810-56-8
pd 110,161
pyranone phosphate
2h-pyran-2-one, 5,6-dihydro-6-(3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraenyl)-
fostriecinum [latin]
ci 920
fostriecin [inn]
cl 1565a
antibiotic ci 920
fostriecine [french]
antibiotic cl 1565a
fostriecina [spanish]
[(1r,3r,4z,6z,8e)-3,10-dihydroxy-1-[(e,1r)-1-hydroxy-1-methyl-3-[(2r)-6-oxo-2,3-dihydropyran-2-yl]allyl]deca-4,6,8-trienyl] dihydrogen phosphate
2h-pyran-2-one, 5,6-dihydro-6-[(1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraenyl]-, (6r)-
87860-39-7
phosphoric acid mono-{3,10-dihydroxy-1-[1-hydroxy-1-methyl-3-(6-oxo-3,6-dihydro-2h-pyran-2-yl)-allyl]-deca-4,6,8-trienyl} ester
chembl17377
bdbm50110690
fostriecinum
fostriecina
unii-zo1648l551
zo1648l551 ,
fostriecine
(+)-fostriecin
2h-pyran-2-one, 5,6-dihydro-6-((1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraenyl)-, (6r)-
fostriecin [who-dd]
2h-pyran-2-one, 5,6-dihydro-6-((1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraen-1-yl)-, (6r)-
(6r)-5,6-dihydro-6-((1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraenyl)-2h-pyran-2-one
SCHEMBL10030539
(6r)-5,6-dihydro-6-[(1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraenyl]-2h-pyran-2-one
DTXSID00868985
Q27295794
fostriecin (sodium salt)
2h-pyran-2-one, 5,6-dihydro-6-[(1e,3r,4r,6r,7z,9z,11e)-3,6,13-trihydroxy-3-methyl-4-(phosphonooxy)-1,7,9,11-tridecatetraen-1-yl]-, (6r)-

Research Excerpts

Overview

Fostriecin (FST, 1) is a natural product with promising antitumor activity produced by Streptomyces pulveraceus. It is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosph atase 4(PP4) found to have anticancer activity in preclinical testing.

ExcerptReferenceRelevance
"Fostriecin (FST, 1) is a natural product with promising antitumor activity produced by Streptomyces pulveraceus. "( Identification of the post-polyketide synthase modification enzymes for fostriecin biosynthesis in Streptomyces pulveraceus.
Kong, RX; Liu, XJ; Niu, MS; Qiu, RG; Tang, L, 2013
)
2.06
"Fostriecin is a natural product purified from Sterptomyces extracts with antitumor activity sufficient to warrant human clinical trials. "( Suppression of Ser/Thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death.
Andrews, JF; Bonness, K; Dean, NM; Honkanen, RE; Huang, X; Musiyenko, A; Theobald, B; Urban, G, 2013
)
2.05
"Fostriecin is a phosphate monoester with excellent antitumor activity against mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. "( Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells.
Ishi, K; Kuramochi, K; Kusayanagi, T; Sugawara, F; Takahashi, N; Takeuchi, T, 2009
)
2.11
"Fostriecin is a unique phosphate monoester antibiotic that was isolated from Streptomyces pulveraceus as a protein phosphatase 2A (PP2A) and PP4A selective inhibitor. "( Elucidation of the biosynthetic gene cluster and the post-PKS modification mechanism for fostriecin in Streptomyces pulveraceus.
Kong, R; Liu, X; Ma, C; Qiu, R; Su, C; Tang, L, 2013
)
2.05
"Fostriecin is a structurally unique, naturally-occurring phosphate monoester that exhibits potent and efficacious antitumor activity."( Fostriecin: chemistry and biology.
Boger, DL; Gauss, CM; Lewy, DS; Soenen, DR, 2002
)
2.48
"Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. "( Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.
Day, A; Eisenhauer, EA; Erlichman, C; Lê, LH; Moore, MJ; Pillon, L; Thiessen, JJ; Wainman, N, 2004
)
2.04
"Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. "( Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay.
Moore, MJ; Pillon, L; Thiessen, JJ, 1994
)
2.07
"Fostriecin is an antitumor drug in phase I clinical trials. "( The antitumor drug fostriecin induces vimentin hyperphosphorylation and intermediate filament reorganization.
Ho, DT; Roberge, M, 1996
)
2.07
"Fostriecin is a novel antitumor antibiotic. "( Fostriecin: a review of the preclinical data.
de Jong, RS; de Vries, EG; Mulder, NH, 1997
)
3.18
"Fostriecin is an inhibitor of topoisomerase II catalytic activity. "( Renal toxicity of the anticancer drug fostriecin.
de Jong, PE; de Jong, RS; de Vries, EG; Meijer, S; Mulder, NH, 1998
)
2.01
"Fostriecin is a unique phosphate monoester which exhibits weak topoisomerase II inhibition (IC(50) = 40 microM) and more potent and selective protein phosphatase 2A and 4 (PP2A and PP4) inhibition (IC(50) = 40-3 nM and 1.5 nM), resulting in mitotic entry checkpoint inhibition."( Total synthesis of fostriecin (CI-920).
Boger, DL; Ichikawa, S; Zhong, W, 2001
)
1.36
"Fostriecin is a new antitumor antibiotic which is being developed further as an anticancer agent based on its marked activity in murine leukemias. "( Inhibition of type II topoisomerase by fostriecin.
Besserer, JA; Boritzki, TJ; Fry, DW; Jackson, RC; Wolfard, TS, 1988
)
1.99

Effects

ExcerptReferenceRelevance
"Fostriecin has a short plasma half-life and longer duration of infusion should be considered."( Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin.
de Jong, RS; de Vries, EG; Groen, HJ; Höppener, FJ; Mulder, NH; Sleijfer, DT; Uges, DR; van der Graaf, WT; Willemse, PH, 1999
)
1.25
"Fostriecin has been reported as having inhibitory activity against DNA topoisomerase type II and protein phosphatases implicated in cell-cycle control."( Fostriecin-mediated G2-M-phase growth arrest correlates with abnormal centrosome replication, the formation of aberrant mitotic spindles, and the inhibition of serine/threonine protein phosphatase activity.
Balczon, R; Cheng, A; Honkanen, RE; Koons, JS; Walsh, AH; Zuo, Z, 1998
)
2.46

Actions

Fostriecin did not cause DNA strand breaks in L1210 cells. It did not stabilize a cleavable complex as do other known inhibitors of this enzyme.

ExcerptReferenceRelevance
"Fostriecin does not inhibit UV-induced excision repair."( Comparison of effects of fostriecin, novobiocin, and camptothecin, inhibitors of DNA topoisomerases, on DNA replication and repair in human cells.
Collins, AR; Gedik, CM, 1990
)
1.3
"Fostriecin did not cause DNA strand breaks in L1210 cells, suggesting that it did not stabilize a cleavable complex as do other known inhibitors of this enzyme."( Inhibition of type II topoisomerase by fostriecin.
Besserer, JA; Boritzki, TJ; Fry, DW; Jackson, RC; Wolfard, TS, 1988
)
1.27

Toxicity

ExcerptReferenceRelevance
" Human BFU-e were greatly inhibited by PZDH, whereas murine BFU-e were relatively resistant to its toxic effects."( Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro.
Du, DL; Grieshaber, CK; Murphy, MJ; Volpe, DA, 1991
)
0.59

Pharmacokinetics

ExcerptReferenceRelevance
" The elimination half-life was 11."( Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay.
Moore, MJ; Pillon, L; Thiessen, JJ, 1994
)
0.63
"We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin."( Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin.
de Jong, RS; de Vries, EG; Groen, HJ; Höppener, FJ; Mulder, NH; Sleijfer, DT; Uges, DR; van der Graaf, WT; Willemse, PH, 1999
)
0.75

Dosage Studied

ExcerptRelevanceReference
" Substitution of C-terminal sequences from the PP2A catalytic subunit produced a chimeric enzyme, CRHM2, that was inhibited by toxins with dose-response characteristics of PP1 and not PP2A."( Importance of the beta12-beta13 loop in protein phosphatase-1 catalytic subunit for inhibition by toxins and mammalian protein inhibitors.
Barik, S; Connor, JH; Honkanen, RE; Kleeman, T; Shenolikar, S, 1999
)
0.3
" No significant difference was seen in PK parameters with repeated dosing during the same cycle."( Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.
Day, A; Eisenhauer, EA; Erlichman, C; Lê, LH; Moore, MJ; Pillon, L; Thiessen, JJ; Wainman, N, 2004
)
0.6
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitorAny EC 3.1.3.* (phosphoric monoester hydrolase) inhibitor that interferes with the action of phosphoprotein phosphatase (EC 3.1.3.16).
bacterial metaboliteAny prokaryotic metabolite produced during a metabolic reaction in bacteria.
topoisomerase II inhibitornull
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
apoptosis inhibitorAny substance that inhibits the process of apoptosis (programmed cell death) in multi-celled organisms.
[role 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]

Drug Classes (7)

ClassDescription
phosphate monoesterAn organic phosphate that is phosphoric acid in which one of the hydrogens is replaced by an organyl group.
polyketideNatural and synthetic compounds containing alternating carbonyl and methylene groups ('beta-polyketones'), biogenetically derived from repeated condensation of acetyl coenzyme A (via malonyl coenzyme A), and usually the compounds derived from them by further condensations, etc. Considered by many to be synonymous with the less frequently used terms acetogenins and ketides.
triolA chemical compound containing three hydroxy groups.
primary allylic alcoholAn allylic alcohol in which the carbon atom that links the double bond to the hydroxy group is also attached to two hydrogens.
2-pyranonesA pyranone based on the structure of 2H-pyran-2-one and its substituted derivatives.
secondary allylic alcoholAn allylic alcohol in which the carbon atom that links the double bond to the hydroxy group is also attached to one other carbon and one hydrogen.
olefinic compoundAny organic molecular entity that contains at least one C=C bond.
[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]

Research

Studies (106)

TimeframeStudies, This Drug (%)All Drugs %
pre-199010 (9.43)18.7374
1990's31 (29.25)18.2507
2000's40 (37.74)29.6817
2010's22 (20.75)24.3611
2020's3 (2.83)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 23.44

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index23.44 (24.57)
Research Supply Index4.69 (2.92)
Research Growth Index4.80 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (23.44)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (1.89%)5.53%
Reviews7 (6.60%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other97 (91.51%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]