You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Creation Date2006-08-13 17:56:48 UTC
Update Date2016-02-11 01:06:44 UTC
Secondary Accession NumbersNone
Metabolite Identification
Common NameLipoxin A4
DescriptionLipoxin A4 (LXA4) was first identified in 1984 by Serhan and colleagues as 5-lipoxygenase interaction product of activated leukocytes. Endogenous transcellular biosynthesis of LXA4 occurs via interaction of leukocytes with epithelium, endothelium or platelets. Lipoxins (LXs) or the lipoxygenase interaction products are generated from arachidonic acid via sequential actions of lipoxygenases and subsequent reactions to give specific trihydroxytetraene-containing eicosanoids. These unique structures are formed during cell-cell interactions and appear to act at both temporal and spatially distinct sites from other eicosanoids produced during the course of inflammatory responses and to stimulate natural resolution. Lipoxin A4 (LXA4) and lipoxin B4 (LXB4) are positional isomers that each possesses potent cellular and in vivo actions. These LX structures are conserved across species. The results of numerous studies reviewed in this work now confirm that they are the first recognized eicosanoid chemical mediators that display both potent anti-inflammatory and pro-resolving actions in vivo in disease models that include rabbit, rat, and mouse systems. LXs act at specific GPCRs as agonists to regulate cellular responses of interest in inflammation and resolution. Aspirin has a direct impact in the LX circuit by triggering the biosynthesis of endogenous epimers of LX, termed the aspirin-triggered 15-epi-LX, that share the potent anti-inflammatory actions of LX. (PMID: 16005201 , 16613568 ).
(5S,6R,15S)-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acidChEBI
(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-Trihydroxy-7,9,11,13-eicosatetraenoic acidChEBI
(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-Trihydroxyeicosa-7,9,11,13-tetraenoic acidChEBI
(7E,9E,11Z,13E)-(5S,6R,15S)-5,6,15-Trihydroxyicosa-7,9,11,13-tetraenoic acidChEBI
5(S),6(R),15(S)-Trihydroxyeicosa-7E,9E,11Z,13E-tetraenoic acidChEBI
5S,6R,15S-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acidChEBI
5S,6R,15S-Trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acidChEBI
5S,6S-Lipoxin a4HMDB
Chemical FormulaC20H32O5
Average Molecular Weight352.4651
Monoisotopic Molecular Weight352.224974134
IUPAC Name(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid
Traditional Namelipoxin A4
CAS Registry Number89663-86-5
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as lipoxins. These are eicosanoids with a trihydroxyicosatetraenoic acid skeleton (a c20-fatty acid, with the chain bearing three hydroxyl groups and four double bonds). Lipoxins have four double bonds, which are all conjugated. In some cases a hydroxyl group is substituted by a C=O group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassEicosanoids
Direct ParentLipoxins
Alternative Parents
  • Lipoxin
  • Long-chain fatty acid
  • Hydroxy fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Secondary alcohol
  • Polyol
  • 1,2-diol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
StatusDetected and Quantified
  • Endogenous
  • Food
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility0.044 mg/mLALOGPS
pKa (Strongest Acidic)4.48ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity104.35 m3·mol-1ChemAxon
Polarizability41.54 Å3ChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Endothelium (Fibroblasts)
  • Epithelium
  • Neutrophil
  • Platelet
PathwaysNot Available
Normal Concentrations
BloodDetected and Quantified<0.00007 uMAdult (>18 years old)Both
BloodDetected and Quantified0.000104 +/- 0.000119 uMAdult (>18 years old)Both
BloodDetected and Quantified<0.00007 uMAdult (>18 years old)Both
BloodDetected and Quantified5.3E-5 +/- 1.3E-5 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BloodDetected and Quantified0.044 +/- 0.0068 uMAdult (>18 years old)Both
Coronary artery disease
Associated Disorders and Diseases
Disease References
Coronary artery disease
  1. Brezinski DA, Nesto RW, Serhan CN: Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. Circulation. 1992 Jul;86(1):56-63. [1617790 ]
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023370
KNApSAcK IDNot Available
Chemspider ID4444429
KEGG Compound IDC06314
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB04385
Metagene LinkHMDB04385
PubChem Compound5280914
PDB IDNot Available
ChEBI ID6498
Synthesis ReferenceRodriguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J. J.; Lee, T. H. Total synthesis of lipoxin A4 and lipoxin B4 from butadiene. Tetrahedron Letters (2000), 41(6), 823-826.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Nicolaou KC, Marron BE, Veale CA, Webber SE, Dahlen SE, Samuelsson B, Serhan CN: Identification of a novel 7-cis-11-trans-lipoxin A4 generated by human neutrophils: total synthesis, spasmogenic activities and comparison with other geometric isomers of lipoxins A4 and B4. Biochim Biophys Acta. 1989 May 15;1003(1):44-53. [2713393 ]
  2. Wu SH, Wu XH, Lu C, Dong L, Chen ZQ: Lipoxin A4 inhibits proliferation of human lung fibroblasts induced by connective tissue growth factor. Am J Respir Cell Mol Biol. 2006 Jan;34(1):65-72. Epub 2005 Sep 1. [16141446 ]
  3. Moores KE, Merritt JE: Lipoxin A4 elevates cytosolic calcium in human neutrophils. Eicosanoids. 1991;4(2):89-94. [1910866 ]
  4. Sumimoto H, Isobe R, Mizukami Y, Minakami S: Formation of a novel 20-hydroxylated metabolite of lipoxin A4 by human neutrophil microsomes. FEBS Lett. 1993 Jan 11;315(3):205-10. [8422907 ]
  5. Bae YS, Park JC, He R, Ye RD, Kwak JY, Suh PG, Ho Ryu S: Differential signaling of formyl peptide receptor-like 1 by Trp-Lys-Tyr-Met-Val-Met-CONH2 or lipoxin A4 in human neutrophils. Mol Pharmacol. 2003 Sep;64(3):721-30. [12920210 ]
  6. Tran U, Boyle T, Shupp JW, Hammamieh R, Jett M: Staphylococcal enterotoxin B initiates protein kinase C translocation and eicosanoid metabolism while inhibiting thrombin-induced aggregation in human platelets. Mol Cell Biochem. 2006 Aug;288(1-2):171-8. Epub 2006 Mar 21. [16550298 ]
  7. Parkinson JF: Lipoxin and synthetic lipoxin analogs: an overview of anti-inflammatory functions and new concepts in immunomodulation. Inflamm Allergy Drug Targets. 2006 Apr;5(2):91-106. [16613568 ]
  8. Andersson P, Serhan CN, Petasis NA, Palmblad J: Interactions between lipoxin A4, the stable analogue 16-phenoxy-lipoxin A4 and leukotriene B4 in cytokine generation by human monocytes. Scand J Immunol. 2004 Sep;60(3):249-56. [15320881 ]
  9. Serhan CN: Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):141-62. [16005201 ]