(±)5 hete

5(S)-HETE, an endogenous metabolite found in the blood, is utilized in researching Rheumatoid Arthritis, Rhinitis, and Asthma [1] [2].

(±)5-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. It contains equal amounts of 5(S)-HETE and 5(R)-HETE. (±)5-HETE induces the aggregation of isolated neutrophils with an IC50 value of 200 nM.[1]

5-HETE ((±)-5-HETE), an oxidative derivative of Arachidonic acid and a fatty acid, comprises a mixture of 5(S)-HETE and 5(R)-HETE. This compound acts as a powerful aggregating agent, effectively inducing neutrophil aggregation with an IC 50 value of 200 nM [1].

5(R)-HETE is a rare lipoxygenase product of arachidonic acid. Nearly all plant and animal 5-LOs produce 5(S)-HETE, but the presence of a 5(R)-LO and the synthesis of 5(R)-HpETE and 5(R)-HETE have been confirmed in oocytes of the bivalve mollusk, S. solidissima. 5(R)-HETE is more potent than the (S)-enantiomer as a chemotactic agent for human neutrophils.

(±)5-HETE, a monohydroxy fatty acid, emerges from the non-enzymatic oxidation of arachidonic acid and is one of six such derivatives. Its methyl ester variant exhibits no unique biological activity and serves as a provided standard. This methyl ester can also be present in oxidatively degraded polyunsaturated fatty acid (PUFA) methyl esters.

5(S)-HETE lactone is a cyclic ester formed by acid-catalyzed nucleophilic addition of the C-5 hydroxyl to the C-1 carboxyl of 5(S)-HETE. The ability of (±)5-HETE lactone to inhibit rat basophilic leukemia cell 5-lipoxygenase (IC50 = 27 μM) may be entirely due to the 5(S) isomer, but the enantiomers have not been tested separately.

Croconazole exhibited dose-dependent inhibitory activity on the 5-lipoxygenase (5-LOX) of neutrophils. Croconazole is an antimycotic agent. The IC50s for the synthesis of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) is 7.8 +/- 1.7 and

5-OxoETE is a polyunsaturated keto acid formed by the oxidation of 5-HETE in human neutrophils by a specific dehydrogenase.[1] It stimulates cytosolic calcium levels in neutrophils with an EC50 value of 2 nM.[2] 5-OxoETE selectively stimulates the migration and degranulation of eosinophils and activates the MAPK pathway in stimulated neutrophils via a specific G protein-coupled receptor.[3],[4],[5],[6]

Mulberrofuran A can inhibit the formations of 12-hydroxy-, 8, 10-heptadecatrienoic acid (HHT) and thromboxane B2, but it can increase the formation of 12-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (12-HETE).

5(S),12(S)-DiHETE is a natural bioactive lipid derived from arachidonic acid . It is synthesized by glycogen-induced rabbit peritoneal polymorphonuclear leukocytes (PMNLs) incubated with AA. 5(S),12(S)-DiHETE can be produced by successive oxygenation of AA by 5-lipoxygenase (5-LO) in platelets and 12-LO in leukocytes. It can also be synthesized from 12(S)-HETE by 5-LO, in the presence of 5-LO activating protein (FLAP), activated with calcium ionophore. 5(S),12(S)-DiHETE is an epimer of leukotriene B4 that is weakly chemotactic for PMNL.

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

5(S),15(S)-DiHETE is synthesized by 15-LO from 5(S)-HETE. It potentiates the degranulation of human PMNL in response to PAF, but not fMLP, calcium ionophore A23187, or LTB4. 5(S),15(S)-DiHETE is chemotactic for eosinophils with an ED50 value of 0.3 μM.

The lipoxins are trihydroxy fatty acids containing a 7,9,11,13-conjugated tetraene. Lipoxin A4 (LXA4) was first described as a metabolite of 15-HpETE and/or 15-HETE when added in vitro to isolated human leukocytes. The material obtained in this manner consists of at least four distinct isomers: 5(S), 6(S); 5(S), 6(R); and the 11-trans and 11-cis isomers of each of these. 6(S)-LXA4 is one of the original four metabolites first identified by Serhan, Nicolaou, and Samuelsson. It was considered to be an artifact by these authors because it lacked the potency of the 5(S),6(R) isomer with respect to contraction of isolated guinea pig lung parenchymal strips. It has not been possible to isolate natural LXA4 from humans or other mammals in amounts sufficient for determination of absolute stereochemistry. Most authors refer to LXA4 as the 5(S)

Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 15(R)-Lipoxin A4 (15(R)-LXA4) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid. [1] [2] 15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA4 demonstrating activity in the nM range.[2] [3] The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 15(R)-LXA4 to regulate leukocyte function.[4] 15(R)-LXA4 is reported to promote resolution of inflammation in LPS-treated stromal cells derived from intermediate-stage diseased supraspinatus tendons as evidenced by increased expression of the STAT-6 pathway target genes, ALOX15 and CD206.[5]

12(S)-HpETE is a monohydroperoxy polyunsaturated fatty acid (PUFA) produced by the action of platelet or leukocyte 12-lipoxygenase (12-LO) on arachidonic acid. It activates human blood leukocyte 5-LO, resulting in the synthesis of 5(S)-HETE, leukotriene B4 (LTB4), and 5(S),12(S)-DiHETE. Rat lung metabolizes 12(S)-HpETE to 8,11,12- and 10,11,12-trihydroxyeicostrienoic acids. 12(S)-HpETE is the mediator of many biological functions, including induction of c-fos and c-jun, activation of AP-1, and endothelium-dependent vasoconstriction. It mediates the inhibitory synaptic response to FMRF-amide in Aplysia sensory neurons and inhibits Ca2+/calmodulin-dependent protein kinase II from rat brain cortex.

15(S)-HpETE is a monohydroperoxy polyunsaturated fatty acid (PUFA) produced by the action of 15-lipoxygenase (15-LO) on arachidonic acid. It is either metabolized to 14,15-leukotriene A4 [1] or reduced to 15(S)-HETE by peroxidases.[2] [1] 15(S)-HpETE mediates a number of biological functions including the induction of c-fos and c-jun, and activation of AP-1. [3] 15(S)-HpETE inhibits prostacyclin synthesis in porcine aortic microsomes and bovine endothelial cells, and can cause the suicide inactivation of porcine 12-LO.[2][4][5]

15-OxoEDE, generated through the oxidation of 15-HEDE, effectively inhibits 5-LO in RBL-1 cells with an IC50 of 55 µM, approximately half as potent as 15(S)-HEDE. Additionally, another related oxo-eicosanoid, 5-oxoETE, is produced from 5(S)-HETE via a specific dehydrogenase, exhibiting significant inflammatory activity.

2,3,5,4'-Tetrahydroxystilbene 2-O-β-D-glucoside (Astragalus polyphenols) is a compound isolated from the roots of Polygonum species, inhibits the formation of 5-HETE, HHT and thromboxane B2.

AHR-5333 mandelate is an anti-allergy compound which has been shown to protect against antigen-induced anaphylactic collapse and ascaris antigen-induced skin hypersensitivity. AHR-5333 mandelate has also been shown to inhibit 5-HETE, LTB4 and LTC4 synthesis.

15(R)-HETE, a monohydroxy fatty acid, is synthesized from arachidonic acid via aspirin-acetylated COX-2, leading to the formation of specialized pro-resolving mediators 15(R)-lipoxin A4 and B4 through a transcellular mechanism involving 5-lipoxygenase (5-LO). Additionally, this compound is produced by the cytochrome P450 (CYP) isoform CYP2C9 and can be generated from arachidonic acid by COX-1 in human mast cells, where it accumulates due to its resistance to conversion into 15-KETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). As an agonist of PPARβ/δ, 15(R)-HETE induces the expression of a target gene in NIH3T3 cells, demonstrating its biological significance.

Hinokiol exhibits anti-inflammatory activity by significantly inhibiting 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) and leukotriene B(4) (LTB4) formations. Additionally, it demonstrates potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

Magnolianin can inhibit strongly (IC50 = 0.45 uM) 5-HETE formation by die cytosol of guinea pig polymorphonuclear leukocytes.