更新于：2024-11-01

5-LOX x PAF receptor

更新于：2024-11-01

基本信息

关联

项与 5-LOX x PAF receptor 相关的药物

CMI-206

靶点

5-LOX x LTB4R x PAF receptor

作用机制

5-LOX抑制剂 [+2]

在研机构-

原研机构

CytoMed, Inc.

在研适应症-

非在研适应症

炎症

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

KC-11404

靶点

5-LOX x PAF receptor

作用机制

5-LOX抑制剂 [+1]

在研机构-

原研机构

Horizon Immobilien GmbH

在研适应症-

非在研适应症

哮喘

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

CMI-392

靶点

5-LOX x PAF receptor

作用机制

5-LOX抑制剂 [+1]

在研机构-

原研机构

CytoMed, Inc.

在研适应症-

非在研适应症

哮喘 [+4]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 5-LOX x PAF receptor 相关的临床结果

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100 项与 5-LOX x PAF receptor 相关的转化医学

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0 项与 5-LOX x PAF receptor 相关的专利（医药）

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项与 5-LOX x PAF receptor 相关的文献（医药）

2018-07-01·International Journal of Biological Macromolecules1区 · 化学

Signaling pathways involved in zymosan phagocytosis induced by two secreted phospholipases A2 isolated from Bothrops asper snake venom in macrophages

1区 · 化学

Article

作者: Gutiérrez, José María ; Teixeira, Catarina ; Zuliani, Juliana Pavan

Phagocytosis, a process involved in host defense, requires coordination of a variety of signaling reactions. MT-II, a catalytically-inactive Lys49-PLA₂¸ and MT-III, an active Asp49-PLA₂ isolated from Bothrops asper snake venom, activate phagocytosis in macrophages. In this study the signal pathways mediating zymosan phagocytosis, focusing in lipidic second messengers, were investigated. Macrophages collected from male Swiss mouse peritoneum were obtained 96h after i.p. injection of thioglycollate. Phagocytosis was evaluated with non-opsonized zymosan in the presence or absence of specific inhibitors. Data showed that both venom PLA₂s increased phagocytosis. Zileuton, Etoricoxib, PACOCF₃ (5-LO, COX-2 and iPLA₂ inhibitors, respectively), as well as WEB2170 (PAF receptor antagonist) significantly reduced phagocytosis induced by both venom PLA₂s. However, Indomethacin (COX-1/COX-2 inhibitor) and Montelukast (CysL receptor antagonist) did not affect the toxins-induced phagocytosis. Moreover, while PACOCF3 (iPLA₂ inhibitor), reduced the phagocytosis induced by MT-II and MT-III, AACOCF₃ (cPLA₂ inhibitor) significantly reduced the MT-II, but not MT-III-induced phagocytosis. These data suggest the effect of both sPLA₂s depends on iPLA₂ and that the effect of MT-II depends on activation of cPLA₂. COX-2 and 5-LO-derived metabolites as well as PAF are involved in the signaling events required for phagocytosis induced by both venom sPLA₂s.

2016-02-01·Biochemical Pharmacology2区 · 医学

Pharmacological inhibition of eicosanoids and platelet-activating factor signaling impairs zymosan-induced release of IL-23 by dendritic cells

2区 · 医学

Article

作者: Montero, Olimpio ; Fernández, Nieves ; Crespo, Mariano Sánchez ; Márquez, Saioa ; Alonso, Sara ; Rodríguez, Mario ; Frade, Javier García

The engagement of the receptors for fungal patterns induces the expression of cytokines, the release of arachidonic acid, and the production of PGE2 in human dendritic cells (DC), but few data are available about other lipid mediators that may modulate DC function. The combined antagonism of leukotriene (LT) B4, cysteinyl-LT, and platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) inhibited IL23A mRNA expression in response to the fungal surrogate zymosan and to a lower extent TNFA (tumor necrosis factor-α) and CSF2 (granulocyte macrophage colony-stimulating factor) mRNA. The combination of lipid mediators and the lipid extract of zymosan-conditioned medium increased the induction of IL23A by LPS (bacterial lipopolysaccharide), thus suggesting that unlike LPS, zymosan elicits the production of mediators at a concentration enough for optimal response. Zymosan induced the release of LTB4, LTE4, 12-hydroxyeicosatetraenoic acid (12-HETE), and PAF C16:0. DC showed a high expression and detectable Ser663 phosphorylation of 5-lipoxygenase in response to zymosan, and a high expression and activity of LPCAT1/2 (lysophosphatidylcholine acyltransferase 1 and 2), the enzymes that incorporate acetate from acetyl-CoA into choline-containing lysophospholipids to produce PAF. Pharmacological modulation of the arachidonic acid cascade and the PAF receptor inhibited the binding of P-71Thr-ATF2 (activating transcription factor 2) to the IL23A promoter, thus mirroring their effects on the expression of IL23A mRNA and IL-23 protein. These results indicate that LTB4, cysteinyl-LT, and PAF, acting through their cognate G protein-coupled receptors, contribute to the phosphorylation of ATF2 and play a central role in IL23A promoter trans-activation and the cytokine signature induced by fungal patterns.

2002-04-15·The Journal of Immunology2区 · 医学

Monocyte Chemoattractant Protein-1 and 5-Lipoxygenase Products Recruit Leukocytes in Response to Platelet-Activating Factor-Like Lipids in Oxidized Low-Density Lipoprotein

2区 · 医学

Article

作者: Castro-Faria-Neto, Hugo C. ; McIntyre, Thomas M. ; Caiado, Lara F. C. ; Marathe, Gopal K. ; Bozza, Patricia T. ; Zimmerman, Guy A. ; Silva, Adriana R. ; de Assis, Edson F. ; Bozza, Marcelo T. ; Prescott, Stephen M.

AbstractOxidized low-density lipoprotein (LDL) contains inflammatory agents, including oxidatively fragmented phospholipids that activate the platelet-activating factor (PAF) receptor, but in vivo events caused by these pathologically generated agents are not well defined. Injection of PAF-like lipids derived from oxidized LDL, or C4-PAF that is a major PAF-like lipid in these particles, into the pleural cavity of mice resulted in rapid monocyte, neutrophil, and eosinophil accumulation. Increased numbers of intracellular lipid bodies in these cells show they were in an inflammatory environment. Leukocyte recruitment was abolished by a PAF receptor antagonist, as expected. PAF-like lipids induced 5-lipoxygenase expression in leukocytes, mRNA expression for monocyte chemoattractant protein-1 (MCP-1) and other chemokines, synthesis of MCP-1, and leukotriene B4. The 5-lipoxygenase inhibitor zileuton impaired neutrophil influx, while MCP-1 had a more global role, as determined with MCP-1−/− mice. The lack of MCP-1 abrogated leukocyte accumulation and lipid body formation both in vivo and in vitro and chemokine transcription in vivo, and reduced in vivo leukotriene B4 production. Thus, PAF-like phospholipids in oxidized LDL induce an inflammatory infiltrate through the PAF receptor, chemokine transcription, lipid body formation, and 5-lipoxygenase expression in leukocytes. MCP-1 has a key role in this inflammatory response, and 5-lipoxygenase products are essential for neutrophil recruitment into the inflamed pleural cavity.