LTB4Leukotriene B4
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Akari is a biopharmaceutical company focused on developing inhibitors of acute and chronic inflammation, specifically for the treatment of rare and orphan diseases, in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together, play a primary role in disease progression.
The development of novel LTA4H modulators to selectively target LTB4 generation.
The company believes that the dual action of Coversin on both C5 and LTB4 may be beneficial in AKC, BP, and aHUS.
PGE2 and LTB4 are synthesized from AA and constitute potent immune mediators, the most important being PGE2, since it has an immunosuppressive effect which inhibits lymphocyte proliferation and NK cells (Garofolo & Petrilli, 2006).
Pain (VAS), NTP, (2007) [16] algometric score, FIQ, BDI, serum PGE2, LTB4, and IL-1 levels Armagan et al.
These compounds include PGP sparing LTB4 inhibitors, classical and alternative complement inhibitors, anti-histamines, and serotonin inhibitors as examples.
Indeed, B-lymphocytes are able to produce the major 5-LOX metabolites 5-HETE and LTB4 in the presence of exogenous arachidonic acid and oxidative stress (Jakobsson et al.
The company said Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing the release of C5a and the formation of C5b-9 (also known as the membrane attack complex or MAC) and independently inhibits LTB4 activity.
In lipid metabolism analysis, BJF decreased the levels of metabolites, such as lecithin, arachidonate, PGE2, LTB4, and 11-epi-PGF2[alpha].
Macrophages secrete tumour necrosis factor alpha (TNF[alpha]), interleukin 8 (Il-8), which is the major neutrophil chemotactic factor in lungs [137], leukotriene B4 (LTB4), monocyte chemotactic protein 1 (MCP-1), matrix metalloproteinases 2, 9, and 12 (MMP-2, MMP-9, and MMP-12), and cathepsins K, L, and S and generate ROS [129,138].
The serum levels of IL-1[beta], IL-6, leukotriene B4 (LTB4), and osteocalcin, and the urine levels of deoxypyridinoline (DPD) were measured using ELISA kits from R&D Systems according to the manufacturer's instructions.
Authors stated previous research that "Prostaglandin E2 is involved in the classic signs of inflammation and possesses both pro-inflammatory and anti-inflammatory actions; thromboxane A2, formed by platelets, macrophages and polymorphonuclear leukocytes, can induce vasoconstriction and promotes aggregation of platelets as well as adhesiveness of polymorphonuclear neutrophils; leukotriene B4 (LTB4) can not only increase vascular permeability and enhance local blood flow by stimulating neutrophil secretion, but also stimulate other inflammatory substances."