12-lipoxygenase

CAY10698 is a 12-lipoxygenase inhibitor (12-LO; IC50 of 5.1 µM).

ML355, a specific, effective 12-Lipoxygenase(12-LOX) inhibitors(IC50=0.34 μM), possess favorable ADME properties.

PF-4191834 is a noniron chelating and non-redox inhibitor of the 5-Lipoxygenase (5-LOX) with an IC50 of 229 nM. PF-4191834 shows ~300-fold selectivity for 5-LOX over 12-LOX and 15-LOX and displays no activity toward the cyclooxygenase enzymes. PF-4191834

NCTT-956 is a potent and specific inhibitor of platelet 12-lipoxygenase (12-LOX) activity.

ML351 is a potent and selective inhibitor of human 15-lipoxygenase-1 (15 LOX)(IC50: 200 nM).

YS121 is a dual inhibitor of microsomal prostaglandin E2 synthase-1 (mPGES-1; IC50=3.4 μM) and 5-lipoxygenase (5-LOX; IC50=6.5 μM). YS121 dose-dependently reduces the production of PGE2 with EC50=12 μM in IL-1β-stimulated A549 cells [1].

2-TEDC is a potent lipoxygenase (LOX) inhibitor with inhibitory effects on 5-LOX, 12-LOX, and 15-LOX with IC50 values of 0.09 μM, 0.013 μM, and 0.5 μM, respectively.2-TEDC can be used in the study of atherosclerosis.

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 is an endogenous metabolite produced by oxidation of ω-6 PUFA dihomo-γ-linolenic acid (DGLA) by 12-lipoxygenase (12-LOX) in platelets, which acts on Gαs-coupled G-protein-coupled receptors, has antithrombotic properties, and has potential therapeutic use in cardiovascular disease. 12(S)-HETrE is reported to inhibit agonist-mediated platelet activation (IC50 = 40 μM), α granule secretion, integrin αIIbβ3 activation, Rap1 activation, and thrombin-induced clot retraction in vitro.

12(S)-HETE, a 12-lipoxygenase metabolite of arachidonic acid, is mitogenic for cancer cell proliferation and enhances angiotensin II-induced contraction of BLT2 (type 2 receptor in arteries of leukotriene B4 mice) and TP (thromboxane receptor)-mediated mechanisms. 12(S)-HETE promotes superoxide and isothromboxane-like metabolites in arterial endothelial cells. production.

12-oxo Leukotriene B4 (12-Oxo-LTB4) is a potent pro-inflammatory lipid mediator classified as a dihydroxy fatty acid that is enzymatically derived from arachidonic acid metabolism via the 5-lipoxygenase (5-LO) pathway, and it promotes a diverse array of leukocyte functional responses including cellular aggregation, stimulation of transmembrane ion fluxes, enhancement of lysosomal enzyme release, superoxide anion generation, chemotaxis, and chemokinesis; 12-oxo Leukotriene B4 is an initial oxidative metabolite formed from Leukotriene B4 via the LTB4 12-hydroxydehydrogenase pathway, which undergoes rapid enzymatic conversion first to 10,11-dihydro-12-oxo-LTB4 followed by reduction of the 12-oxo group to yield 10,11-dihydro-LTB4, and this metabolite exhibits significantly reduced biological potency, being approximately 70-fold less potent than LTB4 in stimulating Ca2+ mobilization in human neutrophils (EC50 = 33 nM vs. 0.46 nM) and also markedly less effective at stimulating neutrophil migration (EC50 = 170 nM vs. 2.7 nM).

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 a highly potent and selective inhibitor of 15-lipoxygenase type 1 (15-LO-1), exhibiting an IC50 of 32 nM in cell-free enzyme assays, with marked selectivity over 15-LO-2, which it does not inhibit, as well as over 5-LO (IC50 = 472 nM) and 12-LO (IC50 = 3,310 nM). BLX3887 selectively suppresses 15-LO metabolite production in eosinophils over neutrophils at 10 μM while additionally inhibiting endocytosis and migration of human peripheral blood mononuclear cell–derived dendritic cells in vitro, highlighting its utility in inflammatory and immune cell signaling research.

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, while 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 leukotriene formation may underlie 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 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-LOE. 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.

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) is a potent 12/15-lipoxygenase (12/15-LO) inhibitor (IC50 = 9-25nm), studied for type 1 diabetes.

ThioLox is a competitive 15-lipoxygenase-1 (15-LOX-1) inhibitor with an IC50 value of 12 μM, demonstrating significant anti-inflammatory and neuroprotective properties, including strong protection against glutamate toxicity.