Page last updated: 2024-12-07

fluorocitrate

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

Description

Fluorocitrate is a potent inhibitor of the enzyme aconitase, which is a key enzyme in the citric acid cycle. It is synthesized by replacing the hydroxyl group at the 2-position of citrate with a fluorine atom. Fluorocitrate binds to the active site of aconitase, blocking the enzyme's activity and preventing the conversion of citrate to isocitrate. This disruption of the citric acid cycle leads to a build-up of citrate and a depletion of energy production. Fluorocitrate has been studied extensively due to its potential as a tool for investigating the role of the citric acid cycle in various biological processes. It has also been investigated as a potential therapeutic agent for treating certain types of cancer, particularly those that rely heavily on the citric acid cycle for energy production. However, its toxicity has limited its clinical application.'

fluorocitrate: competitve inhibitor of aconitase; effects morphology of kidney tubules in fluorocitrate poisoning; RN given refers to cpd with unspecified isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID107647
CHEBI ID174045
SCHEMBL ID679467
MeSH IDM0051110

Synonyms (14)

Synonym
CHEBI:174045
1-luoro-2-hydroxypropane-1,2,3-tricarboxylic acid
fluorocitric acid
fluorocitrate
erythrofluorocitrate (isomer)
2-fluoro-l-erythro-citrate
357-89-1
pentaric acid, 3-c-carboxy-2,4-dideoxy-2-fluoro-
1-fluoro-2-hydroxypropane-1,2,3-tricarboxylic acid
3-c-carboxy-2,4-dideoxy-2-fluoropentaric acid
SCHEMBL679467
Q3497407
DTXSID80957104
1-fluoro-2-hydroxypropane-1,2,3-tricarboxylicacid

Research Excerpts

Overview

3-Fluorocitrate is a substrate for the carboxylate activation half-reaction catalyzed by ATP citrate lyase. It was shown to be a competitive inhibitor of the citrate-binding protein (C protein) of this organism (Ki = 4-5 microM)

ExcerptReferenceRelevance
"3-Fluorocitrate is a substrate for the carboxylate activation half-reaction catalyzed by ATP citrate lyase and induces a net ATPase action during conversion to 3-fluorocitryl-S-coenzyme A."( 3-fluoro-3-deoxycitrate: a probe for mechanistic study of citrate-utilizing enzymes.
Rokita, SE; Srere, PA; Walsh, CT, 1982
)
0.82
"Fluorocitrate was shown to be a competitive inhibitor of the citrate-binding protein (C protein) of this organism (Ki = 4-5 microM)."( Citrate transport in Salmonella typhimurium: studies with 2-fluoro-L-erythro-citrate as a substrate.
Ashton, DM; Kay, WW; Somers, JM; Sweet, GD, 1980
)
0.98

Effects

ExcerptReferenceRelevance
"Fluorocitrate has been shown to be a glial specific metabolic inhibitor."( Contribution of glial metabolism to neuronal damage caused by partial inhibition of energy metabolism in retina.
Nicklas, WJ; Zeevalk, GD, 1997
)
1.02

Actions

ExcerptReferenceRelevance
"Fluorocitrate can inhibit the activation of glial cells in spinal cord and DRG, and reduce MIP."( Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats.
Cao, J; Huang, P; Li, M; Li, Z; Ren, X; Shao, J; Wang, J; Zang, W; Zhang, Z; Zhao, Q, 2014
)
1.85

Treatment

Fluorocitrate treatment of confluent RBE4 cells induced a marked redistribution of the F-actin cytoskeleton from a characteristic marginal band to a more diffuse cytosolic pattern.

ExcerptReferenceRelevance
"Fluorocitrate treatment of confluent RBE4 cells induced a marked redistribution of the F-actin cytoskeleton from a characteristic marginal band to a more diffuse cytosolic pattern."( Effects of energy deprivation induced by fluorocitrate in immortalised rat brain microvessel endothelial cells.
Abbott, NJ; Chan, MW; Rist, RJ; Romero, IA, 1996
)
1.28
"pretreatment with fluorocitrate, an astrocyte inhibitor, restored minocycline- or IL-1ra-induced contralateral MA."( Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain.
Beitz, AJ; Choi, HS; Choi, SR; Han, HJ; Kang, SY; Kim, HW; Kwon, SG; Lee, JH; Moon, JY; Oh, SB; Roh, DH; Yoon, SY, 2015
)
0.74

Toxicity

ExcerptReferenceRelevance
" Fluoroacetate (FA) and its putative toxic metabolite, fluorocitrate (FC), were given to rats and dogs in a series of studies."( Serum citrate as a peripheral indicator of fluoroacetate and fluorocitrate toxicity in rats and dogs.
Bosakowski, T; Levin, AA, 1986
)
0.76
"A series of 1-(di)halo-2-fluoroethanes reported in the literature to be nontoxic or of low toxicity were found to be highly toxic by the inhalation route."( Fluoroacetate-mediated toxicity of fluorinated ethanes.
Keller, DA; Lieder, PH; Roe, DC, 1996
)
0.29

Dosage Studied

ExcerptRelevanceReference
" It is important to realise, however, that the glia-specificity of these compounds depends both on the dosage and on the model used."( Use of fluorocitrate and fluoroacetate in the study of brain metabolism.
Fonnum, F; Hassel, B; Johnsen, A, 1997
)
0.75
" Animals dosed with 1,3-difluoroacetone did not display the 2-3 hour lag phase in either (-)-erythro-fluorocitrate synthesis or in citrate and fluoride accumulation characteristic of animals dosed with 1,3-difluoro-2-propanol."( The mode of toxic action of the pesticide gliftor: the metabolism of 1,3-difluoroacetone to (-)-erythro-fluorocitrate.
Feldwick, MG; Mead, RJ; Menon, KI; Noakes, PS, 2001
)
0.74
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
carbonyl compoundAny compound containing the carbonyl group, C=O. The term is commonly used in the restricted sense of aldehydes and ketones, although it actually includes carboxylic acids and derivatives.
[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 (185)

TimeframeStudies, This Drug (%)All Drugs %
pre-199033 (17.84)18.7374
1990's41 (22.16)18.2507
2000's55 (29.73)29.6817
2010's47 (25.41)24.3611
2020's9 (4.86)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 31.52

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 Index31.52 (24.57)
Research Supply Index5.25 (2.92)
Research Growth Index4.60 (4.65)
Search Engine Demand Index40.78 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (31.52)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews5 (2.65%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other184 (97.35%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]