Chemistry:Eritoran

Short description: Chemical compound

Eritoran

Clinical data
Other names	E 5564
Routes of administration	Intravenous injection
ATC code	none
Identifiers
IUPAC name [(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-phosphonatooxyoxan-2-yl]oxymethyl]-3-(3-oxotetradecanoylamino)oxan-2-yl] phosphoric acid
CAS Number	185955-34-4 N 185954-98-7 (tetrasodium salt)
PubChem CID	6912404
IUPHAR/BPS	4919
DrugBank	DB04933 N
ChemSpider	5288721 N
UNII	551541VI0Y
KEGG	DG01426 N
ChEMBL	ChEMBL501259 N
Chemical and physical data
Formula	C66H126N2O19P2
Molar mass	1313.677 g·mol−1
3D model (JSmol)	Interactive image
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
InChI InChI=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 N Key:BPSMYQFMCXXNPC-MFCPCZTFSA-N N
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Eritoran is a synthetic lipid that inhibits the receptor TLR4. It was developed as a potential treatment for severe sepsis, an excessive inflammatory response to an infection. It failed a five year Phase III clinical trial, the results of which were published in 2013, and as of 2014 was no longer being developed.

It was being developed by the Japanese pharmaceutical company Eisai Co. and was administered intravenously as the sodium salt eritoran tetrasodium.

TLR4 is part of the innate immune system and plays an important role in triggering defense against pathogens. Eritoran is similar in structure to the lipopolysaccharide lipid A - a part of bacteria that binds to TLR4 and activates TLR4, triggering a defense. Eritoran binds to TLR4 but blocks its activation.

Lipid A as found in E. coli, a gram-negative bacterium

Eritoran

Too much signalling by TLR4 may be part of what causes cytokine storms and sepsis, but as of 2021 no drug that inhibits TLR4 has been shown to prevent or treat sepsis or cytokine storms in humans.

Further reading

• "Phase 2 trial of eritoran tetrasodium (E5564), a toll-like receptor 4 antagonist, in patients with severe sepsis". Critical Care Medicine 38 (1): 72–83. January 2010. doi:10.1097/CCM.0b013e3181b07b78. PMID 19661804. 
• "The TLR4 antagonist Eritoran protects mice from lethal influenza infection". Nature 497 (7450): 498–502. May 2013. doi:10.1038/nature12118. PMID 23636320. Bibcode: 2013Natur.497..498S.