Eritoran

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 ; 185954-98-7 (tetrasodium salt);
PubChem CID	6912404;
IUPHAR/BPS	4919;
DrugBank	DB04933 ;
ChemSpider	5288721 ;
UNII	551541VI0Y;
KEGG	DG01426 ;
ChEMBL	ChEMBL501259 ;
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 ; Key:BPSMYQFMCXXNPC-MFCPCZTFSA-N ;
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Short description: Chemical compound

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,^[1]^[2] and as of 2014 was no longer being developed.^[3]

It was being developed by the Japanese pharmaceutical company Eisai Co. and was administered intravenously as the sodium salt eritoran tetrasodium.^[4]

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.^[1]^[4]

Lipid A as found in E. coli, a gram-negative bacterium^[4]

Eritoran^[4]

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.^[1]

References

↑ ^1.0 ^1.1 ^1.2 "Targeting Toll-Like Receptors in Sepsis: From Bench to Clinical Trials". Antioxidants & Redox Signaling 35 (15): 1324–1339. November 2021. doi:10.1089/ars.2021.0005. PMID 33588628.
↑ "Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial". JAMA 309 (11): 1154–1162. March 2013. doi:10.1001/jama.2013.2194. PMID 23512062.
↑ "Strategies to improve drug development for sepsis". Nature Reviews. Drug Discovery 13 (10): 741–758. October 2014. doi:10.1038/nrd4368. PMID 25190187.
↑ ^4.0 ^4.1 ^4.2 ^4.3 "Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies". Expert Opinion on Drug Metabolism & Toxicology 7 (4): 479–494. April 2011. doi:10.1517/17425255.2011.558190. PMID 21323610.

Eritoran

Topic: Chemistry

References

Further reading

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
^NY (what is this?) (verify)