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Identification
NameEritoran
Accession NumberDB04933
TypeSmall Molecule
GroupsInvestigational
Description

Eritoran is a structural analogue of the lipid A portion of lipopolysaccharide (LPS). It is being developed by Eisai Research Institute of Boston for the treatment of severe sepsis.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • E5564
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Eritoran tetrasodium
185954-98-7
Thumb
  • InChI Key: FEMINZOAAWPBPP-RHMAUSBNSA-J
  • Monoisotopic Mass: 1400.770781456
  • Average Mass: 1401.5835
DBSALT001799
CategoriesNot Available
UNII551541VI0Y
CAS number185955-34-4
WeightAverage: 1313.6562
Monoisotopic: 1312.843002884
Chemical FormulaC66H126N2O19P2
InChI KeyBPSMYQFMCXXNPC-MFCPCZTFSA-N
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
IUPAC Name
(11Z)-N-[(2R,3R,4R,5S,6R)-2-{[(2R,3S,4R,5R,6R)-4-(decyloxy)-3-hydroxy-5-[(1-hydroxy-3-oxotetradecylidene)amino]-6-(phosphonooxy)oxan-2-yl]methoxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-5-(phosphonooxy)oxan-3-yl]octadec-11-enimidic acid
SMILES
[H]\C(CCCCCC)=C(/[H])CCCCCCCCCC(O)=N[C@@]1([H])[C@]([H])(OC[C@@]2([H])O[C@]([H])(OP(O)(O)=O)[C@]([H])(N=C(O)CC(=O)CCCCCCCCCCC)[C@@]([H])(OCCCCCCCCCC)[C@]2([H])O)O[C@]([H])(COC)[C@@]([H])(OP(O)(O)=O)[C@]1([H])OCC[C@@]([H])(CCCCCCC)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as acylaminosugars. These are organic compounds containing a sugar linked to a chain through N-acyl group.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassAminosaccharides
Direct ParentAcylaminosugars
Alternative Parents
Substituents
  • Acylaminosugar
  • N-acyl-alpha-hexosamine
  • Disaccharide phosphate
  • O-glycosyl compound
  • Glycosyl compound
  • Disaccharide
  • Monoalkyl phosphate
  • Fatty acyl
  • Alkyl phosphate
  • 1,3-dicarbonyl compound
  • Phosphoric acid ester
  • Oxane
  • Organic phosphoric acid derivative
  • Organic phosphate
  • N-acyl-amine
  • Fatty amide
  • Beta-aminoketone
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Ketone
  • Carboxamide group
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Acetal
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationInvestigated for use/treatment in sepsis and septicemia.
PharmacodynamicsEritoran has been shown to down-regulate the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-alpha in human monocytes.
Mechanism of actionEritoran is a toll-like receptor 4 inhibitor.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingApproximately 55%, primarily to high-density lipoproteins.
MetabolismNot Available
Route of eliminationNot Available
Half life50.4 to 62.7 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9874
Blood Brain Barrier-0.9401
Caco-2 permeable-0.6624
P-glycoprotein substrateSubstrate0.7565
P-glycoprotein inhibitor IInhibitor0.6447
P-glycoprotein inhibitor IIInhibitor0.565
Renal organic cation transporterNon-inhibitor0.9358
CYP450 2C9 substrateNon-substrate0.752
CYP450 2D6 substrateNon-substrate0.8462
CYP450 3A4 substrateSubstrate0.6583
CYP450 1A2 substrateNon-inhibitor0.8413
CYP450 2C9 inhibitorNon-inhibitor0.7925
CYP450 2D6 inhibitorNon-inhibitor0.8903
CYP450 2C19 inhibitorNon-inhibitor0.7586
CYP450 3A4 inhibitorInhibitor0.5831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9351
Ames testNon AMES toxic0.6815
CarcinogenicityNon-carcinogens0.9384
BiodegradationNot ready biodegradable0.7395
Rat acute toxicity2.7745 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8974
hERG inhibition (predictor II)Non-inhibitor0.6143
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00368 mg/mLALOGPS
logP6.81ALOGPS
logP17.14ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)0.5ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area300.61 Å2ChemAxon
Rotatable Bond Count59ChemAxon
Refractivity347.61 m3·mol-1ChemAxon
Polarizability153.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Rossignol DP, Wasan KM, Choo E, Yau E, Wong N, Rose J, Moran J, Lynn M: Safety, pharmacokinetics, pharmacodynamics, and plasma lipoprotein distribution of eritoran (E5564) during continuous intravenous infusion into healthy volunteers. Antimicrob Agents Chemother. 2004 Sep;48(9):3233-40. [PubMed:15328078 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transmembrane signaling receptor activity
Specific Function:
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered b...
Gene Name:
TLR4
Uniprot ID:
O00206
Molecular Weight:
95679.19 Da
References
  1. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO: Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 2007 Sep 7;130(5):906-17. [PubMed:17803912 ]
  2. Shimamoto A, Chong AJ, Yada M, Shomura S, Takayama H, Fleisig AJ, Agnew ML, Hampton CR, Rothnie CL, Spring DJ, Pohlman TH, Shimpo H, Verrier ED: Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury. Circulation. 2006 Jul 4;114(1 Suppl):I270-4. [PubMed:16820585 ]
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Drug created on October 21, 2007 16:23 / Updated on April 29, 2016 21:25