LTB4-IN-2

LTB4-IN-2（Compound 6x）是一种选择性的5-脂氧合酶激活蛋白（FLAP）抑制剂，旨在抑制白三烯B4（LTB4）的形成（IC50：1.15 μM），适用于抗炎研究。

LTB4-IN-1 (Anti-inflammatory agent 2) 是白三烯 (LTB4) 合成抑制剂，IC50 为 70 nM。

Darbufelone mesylate (CI-1004 mesylate) 对细胞中 PGF2α 和 LTB4 产生有抑制作用。Darbufelone mesylate 对 PGHS-2 有抑制作用，IC50 值为 0.19 μM，对 PGHS-1 的IC50 值为 20 μM。

BIIL-260 hydrochloride 是一种具口服活性和高效性的白三烯 B(4) 受体 (LTB4) 拮抗剂，具有抗炎活性，以可饱和、可逆和竞争的方式与 LTB（4） 受体相互作用，抑制 LTB（4） 诱导的人中性粒细胞细胞内 Ca（2+） 释放 。

(±)14(15)-EET is a metabolite of arachidonic acid that is formed via epoxidation of arachidonic acid by cytochrome P450.[1],[2] It prevents increases in leukotriene B4, ICAM-1, and chemokine (C-C motif) ligand 1 (CCL2) induced by oxidized LDL in primary rat pulmonary artery endothelial cells (RPAECs) when used at a concentration of 1 μM.[3] (±)14(15)-EET induces dilation of preconstricted isolated canine coronary arterioles (EC50 = 0.2 pM).[4] It reduces myocardial infarct size as a percentage of the area at risk in a canine model of ischemia-reperfusion injury induced by left anterior descending coronary artery (LAD) occlusion when administered at a dose of 0.128 mg kg prior to occlusion or reperfusion.[5] Reference：[1]. Chacos, N., Falck, J.R., Wixtrom, C., et al. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem. Biophys. Res. Commun. 104(3), 916-922 (1982).[2]. Oliw, E.H., Guengerich, F.P., and Oates, J.A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J. Biol. Chem. 257(7), 3771-3781 (1982).[3]. Jiang, J.-X., Zhang, S.-J., Xiong, Y.-K., et al. EETs attenuate ox-LDL-induced LTB4 production and activity by inhibiting p38 MAPK phosphorylation and 5-LO BLT1 receptor expression in rat pulmonary arterial endothelial cells. PLoS One 10(6), e0128278 (2015).[4]. Oltman, C.L., Weintraub, N.L., VanRollins, M., et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ. Res. 83(9), 932-939 (1998).[5]. Nithipatikom, K., Moore, J.M., Isbell, M.A., et al. Epoxyeicosatrienoic acids in cardioprotection: Ischemic versus reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 291(2), H537-H542 (2006).

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]

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]

Ricinelaidic acid is a 12-hydroxy fatty acid and an antagonist of leukotriene B4 (LTB4) receptors (Ki = 2 μM in porcine neutrophil membranes). It inhibits chemotaxis and calcium flux induced by LTB4 in isolated human neutrophils (IC50s = 10 and 7 μM, respectively). Ricinelaidic acid (1 mg/kg, i.v.) inhibits bronchoconstriction induced by LTB4 in rats by 46%.

11(Z),14(Z)-Eicosadienoic acid methyl ester is a more lipid soluble form of the ω-6 C20-2 fatty acid 11(Z),14(Z)-eicosadienoic acid , a naturally occurring PUFA. 11(Z),14(Z)-Eicosadienoic acid competitively inhibits inosine 5'-monophosphate dehydrogenase (Ki = 3.1 μM) and inhibits the binding of LTB4 to its receptor on neutrophils (Ki = 3.0 μM). Also, serum levels of eicosadienoic acids negatively correlate with degree of sleep disturbance. Eicosadienoic acids are converted by desaturases, in vivo, to eicosatrienoic acids, which are potent vasodilators.

Prostaglandin E2抑制剂3是一种microsomal prostaglandin E合酶-1 (mPGES-1; IC50 = 0.2 µM)的抑制剂，相较于COX-1、COX-2、5-lipoxygenase (5-LO)和soluble epoxide hydrolase (sEH)，在10 µM的无细胞试验中表现出对mPGES-1的选择性。在10 µM和1 µM的浓度下，该抑制剂能抑制A549细胞中IL-1β诱导的PGE2生成以及在J774A.1巨噬细胞中，LPS诱导的IL-6和PGE2生成。同时，它还能抑制由钙离子载体A23187单独或结合花生四烯酸和A23187诱导的5-LO产物形成，包括白三烯B4 (LTB4) 和5-H(p)ETE（IC50s分别为4.9和5.2 µM）。在体内，10 mg/kg剂量的Prostaglandin E2抑制剂3能防止在zymosan诱导的小鼠腹膜炎模型中白细胞渗入腹腔液中。