ltc4

CP-96021 hydrochloride is a potent and orally active antagonist of leukotriene D4 (LTD4) platelet activating factor receptor (Kis: 34 nM and 37 nM).

Leukotriene C4 (LTC4) 是一种类花生酸脂质介质，可调节炎症部位白细胞的募集和功能。Leukotriene C4 是支气管收缩、粘液分泌过多和嗜酸性粒细胞增多的介质，在荨麻疹中具有介导作用。

RG-12525（NID 525） 是一种可口服且具有选择性和竞争性的白三烯 D （LTD）拮抗剂，对 LTC4，LTD4 和 LTE4 诱导的豚鼠薄壁带收缩有抑制作用，IC50 值分别为 2.6 nM，2.5 nM 和 7 nM。RG-12525 对 CYP3A4 有抑制作用， Ki 值为 0.5 µM。RG-12525 是一种新型高效的 PPAR-γ 激动剂（IC50 值约为 60 nM），具有物种特异性，可用于研究哮喘。

AS-35 是一种可口服且具有选择性和高效性的 leukotrienes 拮抗剂，抑制 LTC4，LTD4 和 LTE4 诱导的回肠收缩。AS-35 具有抗过敏作用，抑制白三烯合成。

CI-949 is an allergic mediator release inhibitor, which inhibits leukotriene C4 D4 (LTC4 LTD4), histamine, and thromboxane B2 (TXB2) release (IC50s: 0.5 μM, 11.4 μM and 0.1 μM).

LM-1484 displays a higher affinity for 3H-LTC4 sites and is an antagonist of CysLT1 receptor.

Quinotolast sodium inhibits histamine, LTC4 and PGD2 release in a concentration-dependent manner in the concentration range of 1-100 μg mL.

Nedocromil (FPL 59002) 对多种介质的作用或形成有抑制作用，包括组胺，前列腺素 D2和白三烯 C4。

R112 是 ATP 竞争性的 Syk 激酶抑制剂，它能够抑制 Syk 激酶活性，Ki=6 nM，IC50=226 nM。

Ablukast (Ro 23-3544) 是白三烯受体的选择性拮抗剂，也是LTD4受体拮抗剂。可改善 LTC4 和抗原诱导的支气管狭窄。

AZD9898 是一种白三烯-C4 合成酶抑制剂，IC50 为 0.28 nM。 AZD9898 可用于哮喘研究。 AZD9898 减轻 GABA 结合和肝毒性信号。

Hydrocortisone (Cortisol) 是一种糖皮质激素，由肾上腺素皮质分泌。Hydrocortisone 激动糖皮质激素受体，可促进蛋白质分解代谢、糖异生、毛细血管壁稳定性、肾脏钙排泄，并抑制免疫和炎症反应。

5-O-Demethylnobiletin (5-DEMETHYLNOBILETIN) 是从黄芪中分离出的多甲氧基黄酮，具有抗炎活性，可通过直接抑制 5-LOX 发挥作用，IC50为 0.1 μM。

Pranlukast hemihydrate (ONO-1078 hemihydrate) 是一种具有选择性和高效性的白三烯 （LT）拮抗剂，具有抗哮喘活性，抑制 [3H]LTD4 和 [3H]LTE4 与肺膜的结合，拮抗 LTC4 诱导的豚鼠气管收缩。Pranlukast hemihydrate 可用于研究哮喘。

Pirodomast 是血栓素 A（TXA2）合成酶抑制剂。Pirodomast 能抑制白三烯（LT）D4、C4、E4 的形成和血栓素 B2（TXB2）的活性，但对组胺、甲氧胆碱、血清素、LTC4 或血小板活化因子诱导的豚鼠支气管痉挛的拮抗作用较弱或无效。Pirodomast 在体外对豚鼠气管只有微弱的松弛活性。Pirodomast 是一种潜在的抗过敏化合物，在体外可抑制胰蛋白酶的蛋白水解活性，在体内可阻止抗原诱发过敏绵羊的即时和晚期哮喘反应，抑制抗原诱导的过敏绵羊对组胺和卡巴胆碱的气道高反应性。

Pranlukast (ONO-1078) 是一种半胱氨酰白三烯受体 1 拮抗剂，可拮抗或减少支气管痉挛，用于哮喘研究。

(S)-Verapamil hydrochloride is an inhibitor of leukotriene C4 (LTC4) and calcein transport by MRP1,and leads to the death of potentially resistant tumor cells.

ONO-8809 is a thromboxane A2 receptor antagonist. ONO-8809 inhibited the LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner. Macrophage accumulation and matrix metalloproteinase-9 (MMP-9) activity in the stroke-negative area i

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.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA2α with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and the production of PGE2, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.

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.

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.

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.

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]