12-HETE is the major metabolite of arachidonic acid catalyzed by 12-LOX and inhibits cell apoptosis. 12-HETE promotes the activation and nuclear translocation of NF-κB through the integrin-linked kinase (ILK) pathway. 12-HETE has both antithrombotic and prothrombotic effects. 12-HETE is also a neuromodulator.

Physicochemical Properties

Molecular Formula	C20H32O3
Molecular Weight	320.46628
Exact Mass	320.235
CAS #	71030-37-0
Related CAS #	12-HETE-d8;2525175-25-9
PubChem CID	13786989
Appearance	Colorless to light yellow liquid
Density	1.0±0.1 g/cm3
Boiling Point	487.7±45.0 °C at 760 mmHg
Flash Point	262.8±25.2 °C
Vapour Pressure	0.0±2.8 mmHg at 25°C
Index of Refraction	1.514
LogP	5.45
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	14
Heavy Atom Count	23
Complexity	392
Defined Atom Stereocenter Count	0
SMILES	CCCCC/C=C\CC(/C=C/C=C\C/C=C\CCCC(=O)O)O
InChi Key	ZNHVWPKMFKADKW-VXBMJZGYSA-N
InChi Code	InChI=1S/C20H32O3/c1-2-3-4-5-10-13-16-19(21)17-14-11-8-6-7-9-12-15-18-20(22)23/h7-11,13-14,17,19,21H,2-6,12,15-16,18H2,1H3,(H,22,23)/b9-7-,11-8-,13-10-,17-14+
Chemical Name	(5Z,8Z,10E,14Z)-12-hydroxyicosa-5,8,10,14-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

ln Vitro	12-HETE activates the ILK/NF-κB pathway, which contributes to the suppression of cell apoptosis and suggests a key underlying mechanism that sustains the viability of ovarian cancer cells. 12-HETE promotes cell survival in ovarian cancer via triggering the integrin-linked kinase/NF-κB pathway. 12-HETE exhibits concentration-dependent protection against ovarian cancer cells' apoptosis. 12-HETE (1 µM) dramatically reduces the serum deprivation (SD)-induced caspase-3 activation. With an IC50 value of 1.13 µM, 12-HETE represses the increased activity of caspase-3 produced by SD in a concentration-dependent manner[1]. In ovarian cancer cells, 12-HETE (1 µM) promotes NF-κB activation and nuclear translocation via ILK[1]. 12-HETE causes cell death in human islets, lowers metabolic activity, and decreases insulin secretion. 12-HETE suppresses prostaglandin E1-induced elevation of intracellular cAMP levels while enhancing thrombin-induced bovine platelet aggregation. 12-HETE prevents the aggregation of washed platelets (WP)[2]. 12-HETE has a number of effects on neurons, including a reduction in glutamate release and calcium influx as well as a suppression of AMPA receptor (AMPA-R) activation[3].
Cell Assay	Cell Viability Assay[1] Cell Types: Ovarian cancer OVCAR-3 and SKOV3 cells Tested Concentrations: 0, 0.2, 0.5, and 1 µM Incubation Duration: 0, 24, 48, 72, and 96 hrs (hours) Experimental Results: Inhibited the decrease in cell viability induced by SD in a dose-dependent manner. 1 µM 12-HETE treatment Dramatically mitigated the decrease in cell viability under conditions of SD. Western Blot Analysis[1] Cell Types: Ovarian cancer OVCAR-3 and SKOV3 cells Tested Concentrations: 1 µM Incubation Duration: Experimental Results: Led to increased levels of NF-κB p65 phosphorylation. Caused a significant increase in the protein levels of nuclear NF-κB p65, which was accompanied by diminished levels of NF-κB p65 in the cytoplasm.
ADME/Pharmacokinetics	Metabolism / Metabolites 12-HETE is a known human metabolite of arachidonic acid.
References	[1]. 12-HETE facilitates cell survival by activating the integrin-linked kinase/NF-κB pathway in ovarian cancer. Cancer Manag Res. 2018 Nov 16;10:5825-5838. [2]. Analysis, physiological and clinical significance of 12-HETE: a neglected platelet-derived 12-lipoxygenase product. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 1;964:26-40. [3]. 12-hydroxyeicosatetrenoate (12-HETE) attenuates AMPA receptor-mediated neurotoxicity: evidence for a G-protein-coupled HETE receptor. J Neurosci. 2002 Jan 1;22(1):257-64.
Additional Infomation	(5Z,8Z,10E,14Z)-12-hydroxyicosatetraenoic acid is the (5Z,8Z,10E,14Z)-stereoisomer of 12-HETE. It has a role as a mouse metabolite. It is a conjugate acid of a 12-HETE(1-). 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid is a metabolite generated from arachidonic acid by 12S-type arachidonate 12-lipoxygenase in platelets. 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) may be involved in inflammation and pruritus. A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)

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	3.1204 mL	15.6021 mL	31.2042 mL
	5 mM	0.6241 mL	3.1204 mL	6.2408 mL
	10 mM	0.3120 mL	1.5602 mL	3.1204 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.