Page last updated: 2024-11-11

eritoran

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

Description

eritoran : A lipid A derivative used for the treatment of severe sepsis. [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 CID6912404
CHEMBL ID501259
CHEBI ID68609
SCHEMBL ID10042156
MeSH IDM0500737

Synonyms (27)

Synonym
3-o-decyl-2-deoxy-6-o-{2-deoxy-3-o-[(3r)-3-methoxydecyl]-6-o-methyl-2-[(11z)-octadec-11-enoylamino]-4-o-phosphono-beta-d-glucopyranosyl}-2-[(3-oxotetradecanoyl)amino]-1-o-phosphono-alpha-d-glucopyranose
bdbm50274760
CHEMBL501259 ,
eritoran
chebi:68609 ,
[(2r,3r,4r,5s,6r)-4-decoxy-5-hydroxy-6-[[(2r,3r,4r,5s,6r)-4-[(3r)-3-methoxydecoxy]-6-(methoxymethyl)-3-[[(z)-octadec-11-enoyl]amino]-5-phosphonooxyoxan-2-yl]oxymethyl]-3-(3-oxotetradecanoylamino)oxan-2-yl] dihydrogen phosphate
185955-34-4
3-o-decyl-2-deoxy-6-o-(2-deoxy-3-o-(3-methoxydecyl)-6-o-methyl-2-((1-oxo-11-octadecenyl)amino)-4-o-phosphonoglucopyranosyl)-2-((1,3-dioxotetradecyl)amino)-1-(dihydroxy phosphate)glucopyranose
unii-551541vi0y
551541vi0y ,
eritoran [inn]
3-o-decyl-2-deoxy-6-o-{2-deoxy-3-o-[(3r)-3-methoxydecyl]-6-o-methyl-2-[(11e)-octadec-11-enoylamino]-4-o-phosphonato-beta-d-glucopyranosyl}-2-[(3-oxotetradecanoyl)amino]-1-o-phosphono-alpha-d-glucopyranose
gtpl4919
[(2r,3s,4r,5r,6r)-6-[[(2r,3s,4r,5r,6r)-4-decoxy-3-hydroxy-5-(3-oxotetradecanoylamino)-6-phosphonooxyoxan-2-yl]methoxy]-4-[(3r)-3-methoxydecoxy]-2-(methoxymethyl)-5-[[(z)-octadec-11-enoyl]amino]oxan-3-yl] dihydrogen phosphate
DB04933
eritoran [mi]
3-o-decyl-2-deoxy-6-o-(2-deoxy-3-o-((3r)-3-methoxydecyl)-6-o-methyl-2-((11z)-octadec-11-enoylamino)-4-o-phosphono-.beta.-d-glucopyranosyl)-2-((3-oxotetradecanoyl)amino)-1-o-phosphono-.alpha.-d-glucopyranose
.alpha.-d-glucopyranose, 3-o-decyl-2-deoxy-6-o-(2-deoxy-3-o-((3r)-3-methoxydecyl)-6-o-methyl-2-(((11z)-1-oxo-11-octadecenyl)amino)-4-o-phosphono-.beta.-d-glucopyranosyl)-2-((1,3-dioxotetradecyl)amino)-, 1-(dihydrogen phosphate)
eritoran [who-dd]
SCHEMBL10042156
e5564; eritoran
DTXSID60873217
Q5389586
3-o-decyl-2-deoxy-6-o-[2-deoxy-3-o-[(3r)-3-methoxydecyl]-6-o-methyl-2-[[(11z)-1-oxo-11-octadecenyl]amino]-4-o-phosphono-beta-d-glucopyranosyl]-2-[(1,3-dioxotetradecyl)amino]-alpha-d-glucopyranose1-(dihydrogenphosphat
EX-A5458
CS-0024876
HY-105070

Research Excerpts

Overview

Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site. Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor.

ExcerptReferenceRelevance
"Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. "( Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial.
Aikawa, N; Angus, DC; Chang, CS; Cordasco, E; Dugernier, T; Francois, B; Gogate, J; Jauregui, L; Kalil, AC; Krell, K; LaRosa, SP; Laterre, PF; Lynn, M; Maruyama, T; Mira, JP; Oeyen, S; Opal, SM; Pachl, J; Peckelsen, C; Perrotin, D; Roberts, MB; Rossignol, DP; Schein, R; Takahashi, T; Tidswell, M; Van Nuffelen, M; Vincent, JL; Wheeler, JL; Wittebole, X, 2013
)
2.23
"Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site."( Targeting myeloid differentiation 2 for treatment of sepsis.
Duan, G; Liu, Y; Xu, J; Zhu, J, 2014
)
1.12
"Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor."( Eritoran Suppresses Colon Cancer by Altering a Functional Balance in Toll-like Receptors That Bind Lipopolysaccharide.
Kuo, WT; Lee, TC; Yu, LC, 2016
)
2.6
"Eritoran tetrasodium is a highly effective antagonist of TLR4/MD-2-dependent corneal inflammation."( Inhibition of corneal inflammation by the TLR4 antagonist Eritoran tetrasodium (E5564).
Pearlman, E; Sun, Y, 2009
)
2.04
"Eritoran is a lipid A analogue that competes with LPS for binding to TLR4; however, after intravenous administration, it undergoes a time-dependent deactivation as a consequence of binding to high-density lipoproteins (HDLs)."( Deactivation of the lipopolysaccharide antagonist eritoran (E5564) by high-density lipoprotein-associated apolipoproteins.
Chan, T; Fleischer, JG; Francis, GA; Lynn, M; Rossignol, D; Wasan, KM, 2012
)
1.35
"Eritoran tetrasodium is a nonpathogenic analog of bacterial endotoxin that antagonizes inflammatory signaling by the immune receptor Toll-like receptor-4."( Toll-like receptor-4 antagonist eritoran tetrasodium for severe sepsis.
LaRosa, SP; Tidswell, M, 2011
)
1.37
"Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex."( Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.
Enkhbayar, P; Kim, HM; Kim, JI; Kim, SE; Lee, H; Lee, J; Lee, JO; Matsushima, N; Oh, SC; Park, BS; Yoo, OJ, 2007
)
1.29
"Eritoran (E5564) is a glycophospholipid that acts as a toll-like receptor 4 (TLR4) antagonist that is being tested as a treatment for severe sepsis and septic shock. "( Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.
Chiklis, GR; Lee, SD; Lynn, M; Mason, DX; McShane, J; Risovic, V; Rossignol, DP; Sivak, O; Wasan, KM; Wong, N, 2008
)
2.02

Treatment

Eritoran treatment significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.007) in stimulated HUVECs co-cultured with HC and HS PBMCs. Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h.

ExcerptReferenceRelevance
"Eritoran treatment (50 μg/mL and 100 μg/mL) significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), TNF-α (P = 0.005 and P = 0.003; P = 0.007 and P = 0.005), IL-2 (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IFN-γ (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IL-17A (P = 0.005 and P = 0.002; P = 0.005 and P = 0.002), IL-17F (P = 0.006 and P = 0.006; P = 0.005 and P = 0.005), IL-5 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), IL-9 (P = 0.005 and P = 0.005; P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.007; P = 0.005 and P = 0.005) in stimulated HUVECs co-cultured with HC and HS PBMCs, compared to un-treated condition, respectively."( Decrease in the inflammatory cytokines of LPS-stimulated PBMCs of patients with atherosclerosis by a TLR-4 antagonist in the co-culture with HUVECs.
Doroudchi, M; Kalani, M; Rastegari, B; Talepoor, AG, 2021
)
1.34
"Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. "( Effect of the Toll-like receptor 4 antagonist eritoran on retinochoroidal inflammatory damage in a rat model of endotoxin-induced inflammation.
Alper, M; Ekici, F; Ercan, S; Gülbahar, Ö; Karaca, EE; Korkmaz, S; Or, M; Yüksel, O, 2014
)
2.1
"Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters."( Effect of the Toll-like receptor 4 antagonist eritoran on retinochoroidal inflammatory damage in a rat model of endotoxin-induced inflammation.
Alper, M; Ekici, F; Ercan, S; Gülbahar, Ö; Karaca, EE; Korkmaz, S; Or, M; Yüksel, O, 2014
)
2.1
"Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge."( Novel strategies for targeting innate immune responses to influenza.
Al-Abed, Y; Blanco, JC; Bowie, AG; Calandra, T; Dinarello, CA; Fasano, A; Gusovsky, F; Kurt-Jones, E; Lai, W; Lipsky, M; Pang, C; Patel, MC; Pletneva, LM; Roger, T; Shirey, KA; Tracey, KJ; Vogel, SN, 2016
)
1.16
"Eritoran pretreatment resulted in a reduction in JNK phosphorylation (eritoran versus vehicle: 3.98+/-0.81 versus 7.01+/-2.21-fold increase; P=0.020), less nuclear NF-kappaB translocation (2.70+/-0.35 versus 7.75+/-0.60-fold increase; P=0.00007), and a decrease in cytokine expression (P<0.05)."( Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury.
Agnew, ML; Chong, AJ; Fleisig, AJ; Hampton, CR; Pohlman, TH; Rothnie, CL; Shimamoto, A; Shimpo, H; Shomura, S; Spring, DJ; Takayama, H; Verrier, ED; Yada, M, 2006
)
1.32
"Mice treated with eritoran developed significantly smaller infarcts when compared with mice treated with vehicle alone (21.0+/-6.4% versus 30.9+/-13.9%; P=0.041)."( Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury.
Agnew, ML; Chong, AJ; Fleisig, AJ; Hampton, CR; Pohlman, TH; Rothnie, CL; Shimamoto, A; Shimpo, H; Shomura, S; Spring, DJ; Takayama, H; Verrier, ED; Yada, M, 2006
)
0.92

Pharmacokinetics

In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic (PD) effects in vivo. Plasma eritora's PK parameters were estimated by non-compartmental analysis using the WinNonlin nonlinear estimation program.

ExcerptReferenceRelevance
" In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic (PD) effects in vivo."( Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.
Chiklis, GR; Lee, SD; Lynn, M; Mason, DX; McShane, J; Risovic, V; Rossignol, DP; Sivak, O; Wasan, KM; Wong, N, 2008
)
0.93
" Plasma eritoran pharmacokinetic (PK) parameters were estimated by non-compartmental analysis using the WinNonlin nonlinear estimation program."( Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.
Chiklis, GR; Lee, SD; Lynn, M; Mason, DX; McShane, J; Risovic, V; Rossignol, DP; Sivak, O; Wasan, KM; Wong, N, 2008
)
1.02
" 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

Dosage Studied

ExcerptRelevanceReference
" The purpose of this study was to determine the influence of changes in plasma cholesterol and triglyceride concentrations on the plasma pharmacokinetics and ex vivo activity of eritoran following single intravenous bolus dosing of eritoran to healthy female rabbits fed either a regular chow diet or a cholesterol-enriched diet."( Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.
Chiklis, GR; Lee, SD; Lynn, M; Mason, DX; McShane, J; Risovic, V; Rossignol, DP; Sivak, O; Wasan, KM; Wong, N, 2008
)
0.77
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
lipid AsGlycophospholipids that are the components of endotoxins held responsible for the toxicity of Gram-negative bacteria. Lipid A is the innermost of the three regions of the lipopolysaccharide (LPS) molecule, and its hydrophobic nature allows it to anchor the LPS to the outer membrane. Four acyl chains attached directly to two (1->6)-linked glucosamine sugars are beta-hydroxy acyl chains usually between 10 and 16 carbons in length. Two additional acyl chains are often attached to the beta-hydroxy group.
[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 (5)

Assay IDTitleYearJournalArticle
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.
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.
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.
AID1525540Antagonist activity at TLR4 in human serum assessed as reduction in LPS-induced TNFalpha production after 3 hrs by ELISA2019Journal of medicinal chemistry, 11-27, Volume: 62, Issue:22
Why Some Targets Benefit from beyond Rule of Five Drugs.
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (55)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's9 (16.36)29.6817
2010's43 (78.18)24.3611
2020's3 (5.45)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 33.33

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 Index33.33 (24.57)
Research Supply Index4.13 (2.92)
Research Growth Index5.05 (4.65)
Search Engine Demand Index39.83 (26.88)
Search Engine Supply Index1.91 (0.95)

This Compound (33.33)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (10.91%)5.53%
Reviews9 (16.36%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other40 (72.73%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]