leukotriene

MK-886 (L 663536)是一种细胞可渗透的，具有口服活性的 FLAP (IC50为 30 nM) 和白三烯生物合成 (完整白细胞和人全血中的IC50分别为 3 nM 和 1.1μM) 的抑制剂。它也是一种非竞争性PPARα拮抗剂，可以诱导细胞凋亡。

Montelukast sodium (MK0476) 是可口服的半胱氨酸白三烯受体1 选择性拮抗剂，可用于研究预防哮喘和肝损伤。它还可减少心脏损伤，在肠缺血-再灌注损伤中也具有抗氧化作用。

Montelukast (Singular) 是可口服的半胱氨酸白三烯受体1 选择性拮抗剂，可用于研究预防哮喘和肝损伤。它还可减少心脏损伤，在肠缺血-再灌注损伤中也具有抗氧化作用。

Leukotriene B4 (LTB4) 是一种通过 5-脂氧合酶途径从花生四烯酸衍生而来的化合物，可介导某些炎症和免疫反应。Leukotriene B4 诱导中性粒细胞胞外陷阱阻碍肺孢子菌的清除。

Leukotriene F-4 sulfone induces vascular permeability changes.

Leukotriene B5 (LTB5) is a leukotriene with diverse biological activities. It is a metabolite of eicosapentaenoic acid formed through the 5-lipoxygenase (5-LO) pathway. LTB5 increases contraction of bullfrog lung strips ex vivo in a concentration-dependent manner. In vivo, LTB5 (100 nM) reduces tumor volume in mice injected with Tm1 murine melanoma cells. LTB5 also elicits chemokinesis and lysosomal enzyme release from polymorphonuclear leukocytes (PMNLs) 20- to 30-fold less, and induces platelet aggregation 8-fold less, potently than LTB4 .

Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO pathway. It promotes a number of leukocyte functions including aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme release, superoxide anion production, chemotaxis, and chemokinesis. 12-oxo LTB4 is an initial metabolite of LTB4 formed via the LTB4 12-hydroxydehydrogenase pathway. It is rapidly converted to 10,11-dihydro-12-oxo-LTB4, followed by reduction of the 12-oxo group to give 10,11-dihydro-LTB4. 12-oxo-LTB4 (EC50 = 33 nM) is about 70-fold less potent than LTB4 (EC50 = 0.46 nM) at stimulating Ca2+ mobilization in human neutrophils. It is also significantly less potent than LTB4 at stimulating neutrophil migration with EC50 values of 170 and 2.7 nM for 12-oxo-LTB4 and LTB4, respectively.

Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-lipoxygenase pathway. It promotes a number of leukocyte functions including aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme release, superoxide anion production, chemotaxis, and chemokinesis. At least two LTB4 receptors, termed BLT1 and BLT2, have been identified. 14,15-dehydro LTB4 is a LTB4 receptor antagonist that has a higher binding affinity for BLT1, demonstrating a Ki value of 27 nM, compared to BLT2, which has a Ki value of 473 nM. 14,15-dehydro LTB4 inhibits LTB4-induced release of lysozymes from rat polymorphonuclear leukoctyes with an IC50 value of 1 μM.

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.

11-trans Leukotriene C4 (11-trans LTC4) is a C-11 double bond isomer of LTC4. LTC4 undergoes slow temperature-dependent isomerization to 11-trans LTC4 during storage. 11-trans LTC4 is produced in smaller amounts relative to LTC4 in ionophore-stimulated HMC-1 cells (a human mast cell line) and equine eosinophils, but not in human neutrophils or RBL-1 cells. It is nearly equipotent with LTC4 for contraction of guinea pig parenchymal and ileum. In a radioligand binding assay using guinea pig ileum as a cysteinyl leukotriene receptor preparation, the pKis for LTC4 and 11-trans LTC4 were determined to be 6.42 and 6.58, respectively.

11-trans Leukotriene D4 (11-trans LTD4) is a C-11 double bond isomer of LTD4. LTD4 undergoes slow temperature-dependent isomerization to 11-trans LTD4 during storage. 11-trans LTD4 retains about 10-25 % of the potency for contraction of guinea pig ileum, trachea and parenchyma compared to LTD4. It exhibits an ED50 ranging between 12-60 nM for contraction of guinea pig trachea.

Slow isomerization of the C-11 double bond of LTE4 leads to the formation of 11-trans LTE4. 11-trans LTE4 is equipotent to LTE4 in contracting guinea pig ileum.

Biosynthesis of LTA3 occurs from 5,8,11-eicosatrienoic acid via the 5-LO pathway and it is the putative intermediate in the biosynthesis of 3-series leukotrienes. LTA3 as a free acid is highly unstable. The methyl ester is stable and can be readily hydrolyzed to the free acid as needed.

白三烯A4甲酯可在大鼠肝脏中主要碱性胞质谷胱甘肽转移酶的催化下转化为白三烯C4单甲酯，可用于代谢相关研究。

LTB3 is the LTA hydrolase metabolite of LTA3 in the leukotriene biosynthetic pathway. LTB3 and LTB4 are equipotent in their pro-inflammatory effects. However, LTB3 is five times less potent than LTB4 in eliciting chemotaxis of human neutrophils.

LTB4 dimethyl amide is a moderate inhibitor of LTB4-induced degranulation of human neutrophils (Ki = 130 nM) and lysozyme release from rat PMNL. LTB4 dimethyl amide appears to be an antagonist of the LTB4 receptor on guinea pig lung membranes.

The effects of Leukotriene B4 (LTB4) are mediated by two known receptors, BLT1 and BLT2. LTB4 is a high affinity ligand for BLT1, and many of its pro-inflammatory effects are believed to be transduced through this receptor. The BLT2 is more enigmatic, in that LTB4 is not a high-affinity ligand, nor is it clear that BLT2 activation promotes inflammation. LTB4 ethanolamide (LTB4-EA) is a theoretical 5-LO metabolite of arachidonoyl ethanolamide (AEA). In CHO cells transfected with human BLTR1, LTB4-EA was a potent antagonist with about three times greater affinity for the receptor than LTB4 (Ki = 1.22 nM versus 3.88 nM). LTB4-EA antagonizes the LTB4-induced contractions of guinea pig lung parenchyma with an EC50 of 10 nM. LTB4-EA thus represents a potential endogenous anti-inflammatory compound functioning as a natural antagonist of BLTR1.

Leukotriene C4 (LTC4) is the parent cysteinyl-leukotriene produced by the LTC4 synthase-catalyzed conjugation of glutathione to LTA4. LTC4 is produced by neutrophils, macrophages, and mast cells, and by transcellular metabolism in platelets. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4-induced bronchoconstriction and enhanced vascular permeability contribute to the pathogenesis of asthma and acute allergic hypersensitivity. The concentration of LTC4 required to produce marked contractions of lung parenchymal strips and isolated tracheal rings is about 1 nM. LTC4 methyl ester is a more lipid soluble form of LTC4. The biological activity of LTC4 methyl ester has not been reported.

Leukotriene B4 (LTB4) compounds are produced by both enzymatic and non-enzymatic processes. The products of enzymatic origin, via Leukotriene A4 (LTA4) hydrolase, are stereospecifically 12(R). Non-enzymatic hydrolysis products are 50:50 mixtures at C-12, but are almost exclusively trans at C-6. Thus, the non-enzymatic hydrolysis product of LTA4 is 6-trans-12-epi LTB4. 12-epi LTB4 is an isomer which would not be expected to occur in either non-enzymatic hydrolysis products, or in the enzymatic products of LTA4 hydrolase. Compared to LTB4, 12-epi LTB4 has significantly reduced activity for the LTB4 receptor on human neutrophils (IC50 of 7.5 mM), and on guinea pig lung membranes with a (Ki of 4.7 mM). 12-epi LTB4 is an weak agonist at both the recombinant human BLT1 and BLT2 receptors, requiring approximately 10 mM for full activation of the receptor.

Produced by neutrophils, macrophages, mast cells, and by transcellular metabolism in platelets, leukotriene C4 (LTC4) is the parent cysteinyl leukotriene formed by the LTC4 synthase-catalyzed conjugation of glutathione to LTA4. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4, however, is rapidly metabolized to LTD4 and LTE4, which makes the characterization of LTC4 pharmacology difficult. N-methyl Leukotriene C4 (N-methyl LTC4) is a synthetic analog of LTC4 that is not readily metabolized to LTD4 and LTE4.It acts as a potent and selective CysLT2 receptor agonist exhibiting EC50 values of 122 and > 2,000 nM at the human CysLT2 and CysLT1 receptors, respectively. It has essentially the same potency as LTC4 at both the human and murine receptors CysLT2 receptors. N-methyl LTC4 is potent and active in vivo, causing vascular leak in mice overexpressing the human CysLT2 receptor but not in CysLT2 receptor knockout mice.

20-hydroxy LTB4 is a metabolite of LTB4 in human neutrophils. In human leukocytes, LTB4 is inactivated by the enzyme LTB4 20-hydroxylase. 20-hydroxy LTB4 is not only much less active (~5%) compared to LTB4 in causing degranulation of PMNL, but actually inhibits LTB4-induced degranulation of human neutrophils (Ki = 13.3 nM). However, 20-hydroxy LTB4 is as active as LTB4 in contracting parenchymal strips from guinea pig lung. 20-hydroxy LTB4 retains considerable ligand binding affinity at the BLT2 receptor, but does not appear to function as an agonist.

LTF4 is a cysteinyl-leukotriene produced in vitro, but not reported to date in vivo. It is formed by the incubation of LTE4 with γ-glutamyl transpeptidase and glutathione. LTF4 is a weak agonist in its ability to contract vascular smooth muscle. [1] The rank order of potency of the cysteinyl-leukotrienes to contract vascular smooth muscle is LTD4 > LTC4 > LTE4 >> LTF4. [1] [2]

6-trans-12-epi-Leukotriene B4 是一种花生四烯酸代谢物，是一种有效的抗炎剂。

20-Carboxy-Leukotriene B4 (20-COOH LTB4) 是 Leukotriene B4 (LTB4) 的代谢物。20-Carboxy-Leukotriene B4 以高亲和力与 BLT1 受体结合。20-Carboxy-Leukotriene B4 抑制 LTB4 介导的中性粒细胞反应，迁移、脱粒、白三烯生物合成。