12-lipoxygenase

CAY10698 是选择性的12-Lipoxygenase (12-LOX)抑制剂，IC50=5.1 μM。它对 5-LOX、15-LOX-1、15-LOX-2 和 COX-1 2 无活性。

PF-4191834 是 5-Lipoxygenase (5-LOX) 的非铁螯合和非氧化还原抑制剂，IC50 为 229 nM。 PF-4191834 对 5-LOX 的特异性比 12-LOX 和 15-LOX 高约 300 倍，并且对环氧合酶没有活性。 PF-4191834 可用于炎症和疼痛的研究。

ML351 是一种高度特异的15-LOX-1抑制剂，其 IC50=200 nM。它对 T1D 非肥胖糖尿病小鼠模型的血糖异常和β细胞氧化应激有抑制作用。它对相关同工酶 (5-LOX、血小板 12-LOX、15-LOX-2、绵羊 COX-1 和人 COX-2) 表现出良好的选择性(>250倍)。

ML355 是一种高选择性12-LOX 抑制剂，IC50=0.34 μM，对其他脂氧化酶和环氧化酶有很好的选择性，具有较好的药物动力学特征。

NCTT-956 是一种高效且特异性的血小板 12-脂氧合酶 (12-LOX) 活性抑制剂。

YS121 是微粒体前列腺素 E2 合酶-1 (mPGES-1;IC50=3.4 μM) 和 5-脂氧合酶 (5-LOX;IC50=6.5 μM) 的双重抑制剂。在 IL-1β 刺激的 A549 细胞中，YS121以剂量依赖性地方式减少 PGE2 的产生，EC50为 12 μM。

2-TEDC 是一种有效的脂氧合酶（LOX）抑制剂，对 5-LOX、12-LOX 和 15-LOX 具有抑制作用，IC50 值分别为 0.09 μM、0.013 μM 和 0.5 μM。2-TEDC 可用于研究动脉粥样硬化。

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).

12(S)-HETrE是一种内源性代谢物，由血小板中的12-脂氧合酶（12-LOX）氧化ω-6 PUFA dihomo-γ-linolenic acid(DGLA)产生，作用于Gαs偶联的G蛋白偶联受体，具有抗血栓形成的作用，在心血管疾病具有潜在的治疗作用。12(S)-HETrE 在体外可抑制激动剂介导的血小板活化（IC50 = 40 μM）、α 颗粒分泌、整合素 αⅡbβ3 活化、Rap1 活化和凝血酶诱导的血块回缩。

12(S)-HETE 是花生四烯酸的12-脂氧合酶代谢产物，对癌细胞增殖具有促有丝分裂作用，可增强血管紧张素 II 诱导的 BLT2 收缩（白三烯 B4小鼠动脉中 2 型受体）和 TP （血栓素受体） 介导的机制。12(S)-HETE促进动脉内皮细胞中超氧化物和异血栓素样代谢物的产生。

Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes. The majority of these metabolites are formed through the 5-lipoxygenase (5-LO) pathway. 14,15-LTE4 is a metabolite of 14,15-LTC4 and 14,15-LTD4, an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-LOs on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. These metabolites are classified as eoxins because they are formed mostly by eosinophils. Mast cells and nasal polyps can synthesize 14,15-LTC4 as well, however metabolism to 14,15-LTE4 in these cells and tissue has not been documented. 14,15-LTE4 increases vascular permeability of human endothelial cell monolayers with about 10-fold less potency than LTC4, but approximately 100-fold greater potency than histamine.

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

BLX3887 is an inhibitor of 15-lipoxygenase type 1 (15-LO-1; IC50 = 32 nM in a cell-free enzyme assay).1 It is selective for 15-LO-1 over 15-LO-2, which it does not inhibit, 5-LO (IC50 = 472 nM), and 12-LO (IC50 = 3,310 nM). BLX3887 inhibits the production of 15-LO metabolites selectively in eosinophils over neutrophils when used at a concentration of 10 μM. It also inhibits endocytosis in, and the migration of, isolated human peripheral blood mononuclear cell-derived dendritic cells in vitro. |1. Archambault, A.-S., Turcotte, C., Martin, C., et al. Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO metabolites by human neutrophils and eosinophils. PLoS One 13(8), e0202424 (2018).

13-epi-12-oxo Phytodienoic acid (13-epi-12-oxo PDA) is a lipoxygenase metabolite of α-linolenic acid in the leaves of green plants such as corn. ω-3 and ω-6 polyunsaturated fatty acids in plants are substrates for plant lipoxygenases. 12-oxo PDA is one of the best studied end metabolites of this enzymatic pathway. While the initial enzymatic product and major isomer of 12-oxo PDA contains side chains in the cis position, both being β to the ring, the upper side chain attached at C-13, can and frequently does, isomerize when 12-oxo PDA is extracted, isolated, or stored. 13-epi-12-oxo PDA is the product of this isomerization.

EOS is a ceramide found in the outer layer of the epidermis in mammals. It is comprised of an ω-hydroxy very long-chain ceramide (C28-36) esterified to the essential fatty acid linoleic acid . The consecutive regio- and stereospecific oxygenation of the linoleate portion of EOS by 12(R)-lipoxygenase (12(R)-LO) and eLOX3 is essential for the maintenance of the epidermal barrier to prevent water loss. Following oxygenation, the oxidized linoleate is hydrolyzed, leaving the ω-hydroxy end of the very long-chain fatty acid to covalently bind the protein layer, forming the corneocyte lipid envelope and sealing the gap between the extracellular lipid lamellae and the cornified cell envelope of the corneocyte.

12(S)-HETE is a product of arachidonic acid metabolism through the 12-lipoxygenase pathway. It is primarily found in platelets, leukocytes, and to a lesser extent in smooth muscle cells. It enhances tumor cell adhesion to endothelial cells, fibronectin, and the subendothelial matrix. tetranor-12(S)-HETE is the major β-oxidation product resulting from peroxisomal metabolism of 12(S)-HETE in numerous tissues, and Lewis lung carcinoma cells. No biological function has yet been determined for tetranor-12(S)-HETE. Some data indicate it may play a role in controlling the inflammatory response in injured corneas. In some diseases (e.g., Zellweger's Syndrome) peroxisomal abnormalities result in the inability of cells to metabolize 12(S)-HETE, which may be responsible for symptoms of the disease. The tetranor derivative of 12(S)-HETE is available as a research tool for the elucidation of the metabolic fate of its parent compound.

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.

12(S)-HEPE is a monohydroxy fatty acid synthesized from EPA by the action of 12-LO. Unstimulated neutrophils metabolize 12(S)-HEPE to 12(S),20-diHEPE, whereas stimulated neutrophils produce 5(S),12(S)-HEPE via the 5-lipoxygenase pathway. The competitive action of 12(S)-HEPE with arachidonic acid as a substrate for 5-LO in the formation of leukotrienes may provide a basis for the anti-inflammatory potential of ω-3 fatty acids.

12(S)-HpEPE is a monohydroperoxy polyunsaturated fatty acid produced by the action of 12-lipoxygenase on eicosapentaenoic acid. Although the biological activities of 12(S)-HpEPE have not been well characterized, it is expected to behave similarly to 12(S)-HpETE (Catalog No. 44570).

12(S)-HpETE（12-羟基二十碳四烯酸）是花生四烯酸在12-脂氧合酶（12-LOX）作用下生成的过氧化代谢产物。​能剂量依赖性地刺激细胞内Ca2+释放（效用低于12-HETE），还能通过其对内皮细胞的作用参与血管张力的调节，诱导血管平滑肌细胞c-Fos和c-Jun蛋白的表达，增加AP-1（ activating protein 1）的活性。

12-oxo-13-HOME is an oxylipin derived from linoleic acid .1It is formedviaa 13-HpODE intermediate that is produced by lipoxygenase-mediated metabolism of linoleic acid.2,3,112-oxo-13-HOME has been found in corn and sunflower seedlings.4 1.Ogorodnikova, A.V., Gorina, S.S., Mukhtarova, L.S., et al.Stereospecific biosynthesis of (9S,13S)-10-oxo-phytoenoic acid in young maize rootsBiochim. Biophys. Acta1851(9)1262-1270(2015) 2.Veldink, G.A., and Vliegenthart, J.F.G.The enzymic conversions of 13-hydroperoxy-cis-9-trans-11-octadecadienoic acid into 13-hydroxy-12-oxo-cis-9-octadecenoic acidBiochem. J.110(4)58P(1968) 3.Gardner, H.W.Sequential enzymes of linoleic acid oxidation in corn germ: Lipoxygenase and linoleate hydroperoxide isomeraseJ. Lipid Res.11(4)311-321(1970) 4.Vick, B.A., and Zimmerman, D.C.Levels of oxygenated fatty acids in young corn and sunflower plantsPlant Physiol.69(5)1103-1108(1982)

Cinnamyl-3,4-dihydroxy-α-cyanocinnamate（CDC）是一种强效 12/15-脂氧合酶（12/15-LO）抑制剂(IC50 = 9-25nm)，可用于 1 型糖尿病研究。

ThioLox 是一种竞争性 15-脂氧合酶-1 (15-LOX-1) 抑制剂(IC50值为12 μM)。ThioLox 显示抗炎和神经保护特性。具有抗炎和神经保护作用，对谷氨酸毒性有很强的保护作用。

Baicalein monohydrate is an inhibitor of 12-lipoxygenase, leukotriene biosynthesis and release of lysosomal enzymes. It also inhibits cellular Ca2+ uptake and mobilization and adjuvant-induced arthritis.