Lipoxin A4 (LXA4) is an endogenous lipoxygenase-derived eicosanoid modulator with potent dual anti-inflammatory and pro-anti-inflammatory activities. Lipoxin A4 suppresses the proliferation/growth of human epidermal keratinocytes (NHEK) and the production of inflammatory cytokines/chemokines (such as IL-6, IL-8, etc.) related to the ERK1/2 and NF-kB pathways. Lipoxin A4 inhibits serum amyloid A (SAA)-mediated IL-8 release with IC50 of 25.74 nM.

Physicochemical Properties

Molecular Formula	C20H32O5
Molecular Weight	352.47
Exact Mass	352.224
CAS #	89663-86-5
Related CAS #	Lipoxin A4-d5;1622429-53-1
PubChem CID	5280914
Appearance	Colorless to light yellow liquid
Density	1.1±0.1 g/cm3
Boiling Point	589.4±50.0 °C at 760 mmHg
Flash Point	324.3±26.6 °C
Vapour Pressure	0.0±3.8 mmHg at 25°C
Index of Refraction	1.541
LogP	2.43
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	14
Heavy Atom Count	25
Complexity	451
Defined Atom Stereocenter Count	3
SMILES	[C@@H](O)(/C=C/C=C/C=C\C=C\[C@@H](O)CCCCC)[C@@H](O)CCCC(=O)O
InChi Key	IXAQOQZEOGMIQS-SSQFXEBMSA-N
InChi Code	InChI=1S/C20H32O5/c1-2-3-8-12-17(21)13-9-6-4-5-7-10-14-18(22)19(23)15-11-16-20(24)25/h4-7,9-10,13-14,17-19,21-23H,2-3,8,11-12,15-16H2,1H3,(H,24,25)/b6-4-,7-5+,13-9+,14-10+/t17-,18+,19-/m0/s1
Chemical Name	(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Human Endogenous Metabolite
ln Vitro	In NHEKs, lipoxin A4 (LXA4) suppresses the expression of IL-6 and IL-8[2]. Cyclin D1 expression is downregulated by lipoxin A4[2]. Moreover, lipoxin A4 inhibits NHEKs' NF-kB-p65 nuclear translocation and ERK1/2 phosphorylation[2]. LXA4 (100 nM; 30 minutes of preincubation) suppresses NHEK proliferation either with or without LPS (10 μg/mL) stimulation[2]. In keratinocytes, the LPS-induced secretion and expression of HMGB1 are downregulated by LXA4 pretreatment (100 nM for 30 minutes)[1].
Cell Assay	Cell Proliferation Assay[2] Cell Types: Normal human epidermal keratinocytes (NHEKs) Tested Concentrations: 100 nM Incubation Duration: 30 minutes Experimental Results: A significant increase in proliferation of NHEKs after 7 days of stimulation with LPS (10 μg/mL) was seen. However, there was a significant decrease in the proliferation of NHEKs when pretreated with LXA4 for 30 min. Western Blot Analysis[1] Cell Types: Normal human epidermal keratinocytes (NHEKs) Tested Concentrations: 100 nM Incubation Duration: 30 minutes. Experimental Results: HMGB1 protein levels in the cytoplasm of NHEKs were induced by LPS, which were diminished after preincubation with LXA4 but diminished in the nucleus after stimulation with LPS.
References	[1]. Lipoxin A4 inhibits proliferation and inflammatory cytokine/chemokine production of human epidermal keratinocytes associated with the ERK1/2 and NF-κB pathways. J Dermatol Sci. 2015 Jun;78(3):181-8. [2]. Serum amyloid A opposes lipoxin A₄ to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):935-40. [3]. Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis.Sci Rep. 2017 Aug 2;7(1):7100.
Additional Infomation	Lipoxin A4 is a C20 hydroxy fatty acid having (5S)-, (6R)- and (15S)-hydroxy groups as well as (7E)- (9E)-, (11Z)- and (13E)-double bonds. It has a role as a metabolite and a human metabolite. It is a lipoxin, a long-chain fatty acid and a hydroxy polyunsaturated fatty acid. It is a conjugate acid of a lipoxin A4(1-). lipoxin A4 has been reported in Homo sapiens with data available. Lipoxin A4 is a hydroxy polyunsaturated fatty acid that is a metabolite of arachidonic acid, with potential anti-inflammatory, antifibrinolytic and analgesic activities.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8371 mL	14.1856 mL	28.3712 mL
	5 mM	0.5674 mL	2.8371 mL	5.6742 mL
	10 mM	0.2837 mL	1.4186 mL	2.8371 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.