Eritoran

Identification

Name
Eritoran
Accession Number
DB04933
Type
Small Molecule
Groups
Investigational
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
Synonyms
Not Available
External IDs
E5564
Product Ingredients
IngredientUNIICASInChI Key
Eritoran tetrasodiumFUO195TC7O185954-98-7FEMINZOAAWPBPP-RHMAUSBNSA-J
Categories
UNII
551541VI0Y
CAS number
185955-34-4
Weight
Average: 1313.6562
Monoisotopic: 1312.843002884
Chemical Formula
C66H126N2O19P2
InChI Key
BPSMYQFMCXXNPC-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[[email protected]@]1([H])[[email protected]]([H])(OC[[email protected]@]2([H])O[[email protected]]([H])(OP(O)(O)=O)[[email protected]]([H])(N=C(O)CC(=O)CCCCCCCCCCC)[[email protected]@]([H])(OCCCCCCCCCC)[[email protected]]2([H])O)O[[email protected]]([H])(COC)[[email protected]@]([H])(OP(O)(O)=O)[[email protected]]1([H])OCC[[email protected]@]([H])(CCCCCCC)OC

Pharmacology

Indication

Investigated for use/treatment in sepsis and septicemia.

Structured Indications
Not Available
Pharmacodynamics

Eritoran has been shown to down-regulate the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-alpha in human monocytes.

Mechanism of action

Eritoran is a toll-like receptor 4 inhibitor.

TargetActionsOrganism
UToll-like receptor 4Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Approximately 55%, primarily to high-density lipoproteins.

Metabolism
Not Available
Route of elimination
Not Available
Half life

50.4 to 62.7 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
KEGG Drug
D04043
PubChem Compound
6912404
PubChem Substance
175426908
ChemSpider
5288721
BindingDB
50274760
ChEBI
68609
ChEMBL
CHEMBL501259
HET
E55
PDB Entries
2z65 / 3ula

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedPreventionLeukemias1
2CompletedTreatmentBloodstream Infections / Infection NOS / Sepsis / Shock, Septic / Systemic Inflammatory Response Syndrome (SIRS)1
2SuspendedTreatmentInsulin Sensitivity2
3CompletedTreatmentSevere Sepsis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00368 mg/mLALOGPS
logP6.81ALOGPS
logP17.14ChemAxon
logS-5.6ALOGPS
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Acylaminosugars
Alternative Parents
Hexose phosphates / Disaccharide phosphates / N-acyl-alpha-hexosamines / O-glycosyl compounds / Monoalkyl phosphates / N-acyl amines / 1,3-dicarbonyl compounds / Oxanes / Ketones / Secondary carboxylic acid amides
show 8 more
Substituents
Acylaminosugar / Hexose phosphate / Disaccharide phosphate / N-acyl-alpha-hexosamine / Disaccharide / Glycosyl compound / O-glycosyl compound / Monoalkyl phosphate / Fatty amide / N-acyl-amine
show 24 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
lipid As (CHEBI:68609)

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 ...
Gene Name
TLR4
Uniprot ID
O00206
Uniprot Name
Toll-like receptor 4
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]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 17:27