View source for Chemistry:Eritoran

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 394816802
| IUPAC_name = [(2''R'',3''R'',4''R'',5''S'',6''R'')-4-Decoxy-5-hydroxy-6-<nowiki>[[</nowiki>(2''R'',3''R'',4''R'',5''S'',6''R'')-4-[(3''R'')-3-methoxydecoxy]-6-(methoxymethyl)-3-<nowiki>[[</nowiki>(''Z'')-octadec-11-enoyl]amino]-5-phosphonatooxyoxan-2-yl]oxymethyl]-3-(3-oxotetradecanoylamino)oxan-2-yl] phosphoric acid
| image = Eritoran free acid skeletal.svg

<!--Clinical data-->
| tradename =  
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category =  
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = Intravenous injection

<!--Pharmacokinetic data-->
| bioavailability =  
| protein_bound =  
| metabolism =  
| elimination_half-life =  
| excretion =

<!--Identifiers-->
| IUPHAR_ligand = 4919
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 185955-34-4
| CAS_supplemental = <br />{{CAS|185954-98-7}} (tetrasodium salt)
| ATC_prefix = none
| ATC_suffix =  
| ATC_supplemental =  
| PubChem = 6912404
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB04933
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 551541VI0Y
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 501259
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 5288721
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = DG01426
| synonyms = E 5564

<!--Chemical data-->
| chemical_formula =  
| C=66 | H=126 | N=2 | O=19 | P=2 
| smiles = CCCCCCCCCCCC(=O)CC(=O)NC1C(C(C(OC1OP(=O)(O)O)COC2C(C(C(C(O2)COC)OP(=O)(O)O)OCCC(CCCCCCC)OC)NC(=O)CCCCCCCCCC=CCCCCCC)O)OCCCCCCCCCC
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C66H126N2O19P2/c1-7-11-15-19-22-25-26-27-28-29-30-32-34-38-42-46-57(70)67-60-64(82-49-47-54(80-6)45-41-36-18-14-10-4)62(86-88(73,74)75)56(51-79-5)85-65(60)83-52-55-61(72)63(81-48-43-39-35-24-21-17-13-9-3)59(66(84-55)87-89(76,77)78)68-58(71)50-53(69)44-40-37-33-31-23-20-16-12-8-2/h25-26,54-56,59-66,72H,7-24,27-52H2,1-6H3,(H,67,70)(H,68,71)(H2,73,74,75)(H2,76,77,78)/b26-25-/t54-,55-,56-,59-,60-,61-,62-,63-,64-,65-,66-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = BPSMYQFMCXXNPC-MFCPCZTFSA-N
}}

'''Eritoran''' is a synthetic [[Chemistry:Lipid|lipid]] that inhibits the [[Biology:Receptor (biochemistry)|receptor]] [[Biology:Toll-like receptor 4|TLR4]]. It was [[Medicine:Drug development|developed]] as a potential treatment for severe [[Medicine:Sepsis|sepsis]], an excessive inflammatory response to an [[Medicine:Infection|infection]].  It failed a five year [[Medicine:Phases of clinical research#Phase III|Phase III]] clinical trial, the results of which were published in 2013,<ref name=Chen>{{cite journal | vauthors = Chen F, Zou L, Williams B, Chao W | title = Targeting Toll-Like Receptors in Sepsis: From Bench to Clinical Trials | journal = Antioxidants & Redox Signaling | volume = 35 | issue = 15 | pages = 1324–1339 | date = November 2021 | pmid = 33588628 | pmc = 8817700 | doi = 10.1089/ars.2021.0005 }}</ref><ref>{{cite journal | vauthors = Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, Jauregui L, Krell K, Pachl J, Takahashi T, Peckelsen C, Cordasco E, Chang CS, Oeyen S, Aikawa N, Maruyama T, Schein R, Kalil AC, Van Nuffelen M, Lynn M, Rossignol DP, Gogate J, Roberts MB, Wheeler JL, Vincent JL | display-authors = 6 | title = Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial | journal = JAMA | volume = 309 | issue = 11 | pages = 1154–1162 | date = March 2013 | pmid = 23512062 | doi = 10.1001/jama.2013.2194 | hdl-access = free | hdl = 1854/LU-4222072 }}</ref> and as of 2014 was no longer being developed.<ref name=Fink>{{cite journal | vauthors = Fink MP, Warren HS | title = Strategies to improve drug development for sepsis | journal = Nature Reviews. Drug Discovery | volume = 13 | issue = 10 | pages = 741–758 | date = October 2014 | pmid = 25190187 | doi = 10.1038/nrd4368 | s2cid = 20904332 }}{{Open access}}</ref>

It was being developed by the Japanese pharmaceutical company Eisai Co. and was administered intravenously as the [[Chemistry:Sodium|sodium]] [[Chemistry:Salt|salt]] '''eritoran tetrasodium'''.<ref name=Barochia>{{cite journal | vauthors = Barochia A, Solomon S, Cui X, Natanson C, Eichacker PQ | title = Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 7 | issue = 4 | pages = 479–494 | date = April 2011 | pmid = 21323610 | pmc = 3065179 | doi = 10.1517/17425255.2011.558190 }}</ref>

TLR4 is part of the [[Biology:Innate immune system|innate immune system]] and plays an important role in triggering defense against pathogens. Eritoran is similar in structure to the lipopolysaccharide [[Biology:Lipid A|lipid A]] - a part of bacteria that binds to TLR4 and activates TLR4, triggering a defense. Eritoran binds to TLR4 but blocks its activation.<ref name=Chen/><ref name=Barochia/>   

{| border="0"
| style="vertical-align:top" | [[File:Lipid A.png|thumb|left|[[Biology:Lipid A|Lipid A]] as found in ''E. coli'', a gram-negative bacterium<ref name=Barochia/> ]]
| style="vertical-align:top" | [[File:Eritoran acid skeletal.svg|thumb|left|Eritoran<ref name=Barochia/> ]]
|}

Too much signalling by TLR4 may be part of what causes [[Medicine:Cytokine storm|cytokine storm]]s and sepsis, but as of 2021 no drug that inhibits TLR4 has been shown to prevent or treat sepsis or cytokine storms in humans.<ref name=Chen/> 

== References ==
{{reflist|2}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Tidswell M, Tillis W, Larosa SP, Lynn M, Wittek AE, Kao R, Wheeler J, Gogate J, Opal SM | display-authors = 6 | title = Phase 2 trial of eritoran tetrasodium (E5564), a toll-like receptor 4 antagonist, in patients with severe sepsis | journal = Critical Care Medicine | volume = 38 | issue = 1 | pages = 72–83 | date = January 2010 | pmid = 19661804 | doi = 10.1097/CCM.0b013e3181b07b78 | s2cid = 19160973 }}
* {{cite journal | vauthors = Shirey KA, Lai W, Scott AJ, Lipsky M, Mistry P, Pletneva LM, Karp CL, McAlees J, Gioannini TL, Weiss J, Chen WH, Ernst RK, Rossignol DP, Gusovsky F, Blanco JC, Vogel SN | display-authors = 6 | title = The TLR4 antagonist Eritoran protects mice from lethal influenza infection | journal = Nature | volume = 497 | issue = 7450 | pages = 498–502 | date = May 2013 | pmid = 23636320 | pmc = 3725830 | doi = 10.1038/nature12118 | bibcode = 2013Natur.497..498S }}
{{refend}}

[[Category:Immunosuppressants]]

{{Sourceattribution|Eritoran}}