15-hete

(±)15-HETE is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1].

1-Stearoyl-2-15(S)-HETE-sn-glycero-3-PE is a phospholipid that contains stearic acid at the sn-1 position and 15(S)-HETE at the sn-2 position. It is formed in human peripheral monocytes activated by the calcium ionophore A23187 by direct oxidation of 1-stearoyl-2-arachidonoyl-sn-glycero-3-PE by 15-LO. Phosphoethanolamine (PE) HETEs (PE-HETEs), including 1-stearoyl-2-15(S)-HETE-sn-glycero-3-PE, are the main source of esterified HETE in ionophore-activated monocytes.

15(S)-HETE methyl ester is a synthetic derivative of 15(S)-HETE , a major arachidonic acid metabolite from the 15-lipoxygenase pathway. Methyl esters of lipids are commonly used in formulations of nutritional supplements.

1-Stearoyl-2-15(S)-HETE-sn-glycero-3-PC is a phospholipid that contains stearic acid at the sn-1 position and 15(S)-HETE at the sn-2 position. It is produced via oxidation of 1-stearoyl-2-arachidonoyl-sn-glycero-3-PC by 15-lipoxygenase (15-LO).

20-HETE Intermediate 15 是20-羟基二十碳四烯酸的中间体。

CAY10397, a selective inhibitor of 15-hydroxy PGDH, significantly suppresses endogenous 11-oxo-ETE production with a corresponding increase in 11(R)-HETE.

N-Arachidonoyl taurine is an arachidonoyl amino acid. It is oxygenated by 12(S)- and 15(S)-lipoxygenase and is converted to 12-HETE-taurine (12-HETE-T) in murine resident peritoneal macrophages. N-Arachidonoyl taurine is an activator of the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 (EC50s = 28 and 21 μM, respectively). It increases calcium flux in HIT-T15 pancreatic β-cells and INS-1 rat islet cells when used at a concentration of 10 μM and increases insulin secretion from 832 13 INS-1 pancreatic β-cells. The levels of N-arachidonoyl taurine are changed in mouse brain following administration of δ9-tetrahydrocannabinol (δ9-THC).

15-OxoETE is produced by oxidation of the 15-hydroxyl of 15-HETE. Whether this is a major pathway of 15-HETE metabolism is yet to be clearly established.

Lipoxin A4 methyl ester (LXA4 methyl ester) is a more lipid soluble, prodrug formulation of the transcellular metabolite LXA4. LXA4 is a trihydroxy fatty acid containing a conjugated tetraene, produced by the metabolism of 15-HETE or 15-HpETE with human leukocytes.[1] LXA4 is equipotent to leukotriene B4 (LTB4) in inducing superoxide generation in human neutrophils at 0.1 μM.[2] LXA4 is associated with several other biological functions including leukocyte activation, chemotaxis effects, natural killer cell inhibition, and monocyte migration and adhesion.[2],[3],[4]

CAY10770 is an inhibitor of the cytochrome P450 (CYP) isoform CYP4Z1 (IC50= 5.9 μM).1It is selective for CYP4Z1 over CYP4A11, CYP4F2, CYP4F3a, CYP4F3b (IC50s = 187-282 μM) but does inhibit CYP4F8 and CYP4F12 (IC50s = 167 and 91 μM, respectively). CAY10770 (3 μM) inhibits the production of 14(15)-EET, 19-HETE, and 14(15)-DiHET by 83, 86, and 80%, respectively, in T47D breast cancer cells expressing CYP4Z1. 1.Kowalski, J.P., McDonald, M.G., Pelletier, R.D., et al.Design and characterization of the first selective and potent mechanism-based inhibitor of cytochrome P450 4Z1J. Med. Chem.63(9)4824-4836(2020)

(5Z,11Z,15R)-15-Hydroxyeicosa-5,11-dien-13-ynoic acid is a stable isomer of 15(S)-HETE , a major arachidonic acid metabolite from the 15-lipoxygenase pathway. (5Z,11Z,15R)-15-Hydroxyeicosa-5,11-dien-13-ynoic acid elicits concentration-dependent contraction of isolated pulmonary arteries from rabbits and inhibits the proliferation and migration of hormone-independent prostate carcinoma PC-3 cells.

8(S),15(S)-DiHETE is formed when 15(S)-HETE is subjected to further oxidation by 15-LO. It causes eosinophil chemotaxis with an ED50 value of 1.5 μM but is not chemotactic for neutrophils. 8(S),15(S)-DiHETE antagonizes the hyperalgesic activity of 8(R),15(S)-DiHETE and LTB4 in the rat hind paw pain model.

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]

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)

Lipoxin B4是花生四烯酸的代谢产物，能够抑制上呼吸道中的鼻粘膜中的白细胞浸润和粘液分泌，具有粘膜保护作用，常用于研究上、下呼吸道的过敏性炎症。

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.

13(S)-HODE is the lipoxygenase metabolite of linoleic acid. 13(S)-HODE modulates the platelet-activating factor, leukotriene B4, and formyl-Met-Leu-Phe-induced calcium influx in human polymorphonuclear leukocytes. The mechanism by which 13(S)-HODE elicits its inhibitory effect is still unclear. The use of biotinylated 15(S)-HETE as a probe for detecting binding proteins and/or receptors that specifically bind 15(S)-HETE provides a basis for similar use of 13(S)-HODE-biotin.

Lipoxin B4 (LXB4) methyl ester is a lipid soluble prodrug form of the transcellular metabolite LXB4 . LXB4 is a positional isomer of LXA4 produced by the metabolism of 15-HETE or 15-HpETE by human leukocytes. At a concentration of 100 nM, LXB4 inhibits polymorphonuclear leukocyte (PMN) migration stimulated by leukotriene B4 and inhibits LTB4-induced adhesion of PMNs with an IC50 value of 0.3 nM.

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.

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.

CYP4A11 CYP4F2-IN-2（compound 15）作为一种口服抑制剂，其针对CYP4A11及CYP4F2 的IC50s 分别为 120 nM 和 220 nM。该化合物能够有效抑制大鼠肾中的20-HETE生成，显示出对尿病肾病和常染色体显性多囊肾病治疗的潜力。