pmn

CU-6PM is a new fluorescent RXR agonist. CU-6PMN was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay CU-6PMN enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration.

CV-6209 is a potent antagonist of the platelet-activating factor (PAF) receptor.

U-73122 (U73122) , an effective PLC inhibitor, reduces agonist-induced Ca2+ increases in platelets and PMN.

AZ084 is a potent, selective, allosteric, and orally active CCR8 antagonist (Ki: 0.9 nM) with potential to treat asthma.

Resolvin E1 is an effective endogenous pro-resolving mediator of inflammation. Resolvin E1 has unique counterregulatory actions that inhibit PMN transendothelial migration. Resolvin E1 also acts as an effective inhibitor of leukocyte infiltration, dendrit

D-Citrulline (H-D-Cit-OH), a stereoisomer of L-citrulline, effectively reduces cardiac contractile dysfunction caused by polymorphonuclear leukocyte (PMN) in isolated perfused rat hearts undergoing ischemia reperfusion. This protective effect is mediated through a non-NO-mediated mechanism.

N-Formyl-MMYALF is an effective mitochondrial N-formyl peptide (mtFP) that possesses activity in depleting calcium ions from the endoplasmic reticulum. Additionally, it inhibits the PMN chemotactic response to bacterial peptides mediated by FPR-1.

N-Formyl-MMYALF TFA is a mitochondrial N-formyl peptide known for its ability to deplete calcium ions in the endoplasmic reticulum. Additionally, it inhibits the FPR-1-mediated chemotactic response of PMNs to bacterial peptides.

6-OAU (GTPL5846)(GTPL5846; 6-n-octylaminouracil) is a surrogate agonist of GPR84; activates human GPR84 in the presence of Gqi5 chimera in HEK293 cells with an EC50 of 105 nM in the PI assay.

inhibits leukotriene B4 (LTB4)-induced polymorphonuclear neutrophils (PMN) chemotaxis

TCV-309 is an inhibitor of platelet activating factor (PAF). TCV-309 reduces graft PMN infiltration and enhances early function of 24-hour-preserved rat kidneys with long warm ischemia. TCV-309 attenuates the priming effects of bronchoalveolar macrophages

MK-287 (L-680573) is a platelet activator (PAF) antagonist that effectively inhibates the binding of [3H]C18-PAF to human platelets, polynucleated white blood cells (PMN), and pulmonary membranes. May be used to treat asthma,

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]

17(R)-Protectin D1 is an aspirin-triggered epimer of the specialized pro-resolving mediator protectin D1 .1It decreases leukotriene B4-induced transendothelial migration of human polymorphonuclear (PMN) neutrophils when used at concentrations ranging from 0.1 to 10 nM. 17(R)-Protectin D1 (0.01-10 ng) reduces the recruitment of neutrophils in a mouse model of TNF-α-induced peritonitis. 1.Serhan, C.N., Fredman, G., Yang, R., et al.Novel proresolving aspirin-triggered DHA pathwayChem. Biol.18(18)976-987(2011)

Resolvin conjugate in tissue regeneration 1 (RCTR1) is a specialized pro-resolving mediator (SPM) biosynthesized from docosahexaenoic acid by isolated human macrophages and apoptotic polymorphonuclear (PMN) neutrophils.1It has been found in human spleen and bone marrow.2RCTR1 is produced via lipoxygenase-mediated oxidation of DHA to 7(S)-8-epoxy-17(S)-HDHA, which is conjugated to glutathione.1,2,3RCTR1 (10 nM) increases phagocytosis ofE. colior apoptotic neutrophils in isolated human monocyte-derived macrophages.2It decreases chemotaxis induced by leukotriene B4in isolated human neutrophils when used at a concentration of 10 nM. RCTR1 (1 and 10 nM) accelerates tissue regeneration in planaria. Intraperitoneal administration of RCTR1 (100 ng/animal) shortens the inflammatory resolution period and decreases inflammatory exudate neutrophil infiltration in a mouse model ofE. coli-induced peritonitis. 1.Dalli, J., Ramon, S., Norris, P.C., et al.Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathwaysFASEB J.29(5)2120-2136(2015) 2.de la Rosa, X., Norris, P.C., Chiang, N., et al.Identification and complete stereochemical assignments of the new resolvin conjugates in tissue regeneration in human tissues that stimulate proresolving phagocyte functions and tissue regenerationAm. J. Pathol.188(4)950-966(2018) 3.Rodriguez, A.R., and Spur, B.W.First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugatesTetrahedron Lett.58(16)1662-1668(2017)

Docosahexaenoic acid is a nutritionally-derived ω-3 fatty acid that is abundant in the brain and the retina and is thought to be important in early development and for therapeutic approaches to inflammatory disorders and cancer. 14(S)-HDHA is an oxygenation product of DHA that serves as a precursor to maresin 1 , an anti-inflammatory, pro-resolving mediator that prevents polymorphonuclear neutrophil (PMN) infiltration and stimulates macrophage phagocytosis. At doses as low as 0.2 ng/mouse 14(S)-HDHA administration resulted in reduced infiltration of PMNs into sites of inflammation.

Lipoxin B4 (LXB4) is a positional isomer of LXA4 produced by the metabolism of 15-HETE or 15(S)-HpETE by human leukocytes. At 100 nM, LXB4 inhibits polymorphonuclear leukocyte (PMN) migration stimulated by leukotriene B4 and inhibits LTB4-induced PMN adhesion with an IC50 value of 0.3 nM.

Resolvin E4 (RvE4) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acid by 15-lipoxygenase (15-LO)via15(S)-HpEPE and 15S-hydroxy, 5S-HpEPE intermediatesin vitroand by isolated human M2 macrophages or polymorphonuclear (PMN) neutrophils under normoxic or hypoxic conditions. RvE4 synthesis is enhanced in M2 macrophage and neutrophil co-cultures, indicating transcellular biosynthesis by a potential 15-LO and 5-LO mechanism. It has been found in mouse inflammatory exudates. RvE4 (10 nM) increases efferocytosis of apoptotic neutrophils or senescent red blood cells (sRBCs) by human M2 macrophages under hypoxic conditionsin vitro. Intraperitoneal administration of RvE4 (100 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of hemorrhagic peritonitis induced by zymosan A and thrombin. It also increases inflammatory exudate macrophage infiltration and efferocytosis of apoptotic neutrophils and/or RBCs in the same model. 1.Norris, P.C., Libreros, S., and Serhan, C.N.Resolution metabolomes activated by hypoxic environmentSci. Adv.5(10)eaax4895(2019)

Lipoxin B4 (LXB4) methyl ester is a lipid-soluble prodrug form of the transcellular metabolite LXB4, which is a positional isomer of LXA4 produced by the metabolism of 15-HETE or 15-HpETE by human leukocytes. At 100 nM, LXB4 inhibits polymorphonuclear leukocyte (PMN) migration stimulated by leukotriene B4 and inhibits LTB4-induced adhesion of PMNs with an IC50 of 0.3 nM.

Flufenamic acid-d4 is intended for use as an internal standard for the quantification of flufenamic acid by GC- or LC-MS. Flufenamic acid is a non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor (IC50s = 3 and 9.3 µM for human COX-1 and COX-2, respectively). Flufenamic acid inhibits TNF-α-induced increases in COX-2 levels and NF-κB activation in HT-29 colon cancer cells in a concentration-dependent manner. It inhibits calcium influx induced by fMLP or A23187 in human polymorphonuclear leukocytes (PMN) with IC50 values of 29 and 14 µM, respectively. Flufenamic acid also activates various ion channels, including transient receptor potential canonical 6 (TRPC6) and the large-conductance calcium-activated potassium channel (KCa1.1). It also inhibits various ion channels, including TRPC3 and the cystic fibrosis transmembrane conductance regulator (CFTR). Flufenamic acid (20 mg kg) reduces increases in intestinal fluid secretion and intestinal barrier disruption in mice ......

PMX-53, a macrocyclic complement 5a (C5a) peptidomimetic and C5a receptor antagonist (IC50 = 0.3 µM), effectively inhibits the C5a-induced secretion of myeloperoxidase (MPO) in isolated human polymorphonuclear leukocytes (PMNs). Administered orally at 10 mg kg, PMX-53 mitigates vascular leakage, PMN infiltration, and the production of TNF-α and IL-6 in a rat peritoneal Arthus reaction model. Additionally, in a 3-nitropropionic acid (3-NP)-induced Huntington's disease rat model, it alleviates body weight loss, anorexia, and striatal degeneration. Furthermore, at a dose of 3 mg kg, PMX-53 decreases atherosclerotic lesion size and lipid content in ApoE- - mice.

[Glu1]-Fibrinopeptide B, a derivative of fibrinopeptide B amino acid residues 1-14, originates from human fibrinopeptide B (hFpB). hFpB is a proteolytic cleavage product of the fibrinogen B beta-chain, specifically generated by thrombin, which plays a significant role in activating neutrophils (PMN), monocytes, and fibroblasts.