degranulation

(R)-Citronellol ((R)-(+)-β-Citronellol) is found in herbs and spices, as well as bilberry. (R)-Citronellol is a constituent of black cumin (Nigella sativa) seeds. (R)-Citronellol is a common constituent of plant oils, especially in the Rutaceae.

PKC ζ pseudosubstrate acetate is an inhibitor of protein kinase C (PKC) ζ; attached to cell permeabilisation Antennapedia domain vector peptide. Consists of amino acids 113 - 129 of PKC ζ pseudosubstrate domain linked by a disulphide bridge to the Antenna

Meclofenamate sodium is a potent non-steroidal anti-inflammatory agent, which can specifically inhibit chemokine-induced human polymorphonuclear leukocyte function: chemotaxis, degranulation, and superoxide anion free radical production.

8 Hydroxy PIPAT oxalate is a selective 5-HT1A receptor agonist that enhances the spontaneous release of histamine by promoting the degranulation of mast cells in guinea pig and human intestinal preparations. By activating the serotonin signaling pathway, this compound demonstrates potential in regulating gastrointestinal functions and offers insight into the management and suppression of functional gastrointestinal disorders such as irritable bowel syndrome. Its effects in increasing histamine release could play a crucial role in gastrointestinal regulation.

Histamine glutarimide is a novel small molecule agent functioning as an inhibitor of glutaminyl-peptide cyclotransferase (QPCT), which targets key inflammatory processes including eosinophilic migration and mast cell degranulation, Histamine glutarimide has demonstrated significant anti-asthmatic effects in various preclinical animal models of allergic asthma.

GE1111 is an antagonist of the mas-related G protein-coupled receptor X2 (MRGPRX2), exhibiting an IC50 of 9.42 μM. It inhibits mast cell degranulation with an IC50 of 4.7 μM. In the C48/80-induced systemic allergic reaction model, GE1111 demonstrates both antiallergic and anti-inflammatory properties.

Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.

Mrgx2 antagonist-3 (Compound B-40) is a highly selective antagonist of the MrgX2 receptor, with an IC50 range of 0.042-2.5 nM. It blocks downstream G protein signaling and β-arrestin recruitment, inhibiting Mrgx2 receptor-mediated calcium influx and cell degranulation. Mrgx2 antagonist-3 shows potential for research in inflammation-associated diseases and pruritus, such as chronic urticaria and allergic asthma.

BER-5 is a potent MrgX2 antagonist, demonstrating broad-spectrum antagonistic activity against various MrgX2 agonists. It can inhibit Substance P(SP)-induced degranulation in LAD2 cells and alleviate SP-induced allergic reactions in mice. BER-5 is useful for researching mechanisms related to allergic reactions.

MrgprX2-IN-1 (Compound 2-10) is a selective antagonist of the Mas-related G protein-coupled receptor X2 (MRGPRX2). It functions by inhibiting mast cell degranulation and the release of inflammatory mediators mediated by MRGPRX2, thereby blocking non-IgE-dependent immune responses. MrgprX2-IN-1 holds potential for research into pseudo-allergic reactions, chronic pruritus, and inflammatory diseases.

MrgprX2-IN-2 (Compound example 12) is a selective antagonist of the Mas-related G protein-coupled receptor X2 (MRGPRX2). It works by inhibiting MRGPRX2-mediated mast cell degranulation and the release of inflammatory mediators, thus blocking non-IgE-dependent immune responses. MrgprX2-IN-2 shows potential for research in the areas of pseudo-allergic reactions, chronic pruritus, and inflammatory diseases.

APC 366 is a selective tryptase inhibitor (Ki = 7.1 μM). Tryptase is a serine protease released during mast cell degranulation, which reduces acute airway responses to allergens and can be used for asthma allergy treatment.

Cariporide (HOE-642) (HOE-642), an effective NHE1 inhibitor, has inhibitory effects on the degranulation of human platelets, the formation of platelet-leukocyte-aggregates, and the activation of the GPIIb/IIIa receptor (PAC-1).

(R)-ZINC-3573 is a potent and highly selective MRGPRX2 probe that activates endogenous MRGPRX2 in a human mast cell line, inducing degranulation and calcium release.

Neuromedin C is a bombesin-like neuropeptide that stimulates uterine smooth muscle contraction and the release of gastrin , somatostatin, and amylase in rats. Neuromedin C is a truncated form of gastrin-releasing peptide corresponding to the GRP amino acids 18-27. It inhibits GRP and bombesin binding to rat pancreatic membranes (IC50s = 0.4 and 2.2 nM, respectively), which can be reduced by sodium chloride and guanylyl imidodiphosphate . Neuromedin C induces scratching and mast cell degranulation in mice when administered intradermally at doses ranging from 1 to 300 nmol/site, which is inhibited by the BB2 bombesin receptor agonist RC-3095 and reduced in mast cell-deficient mice. Neuromedin C (3.2 nmol/kg, i.p.) reduces rat glucose consumption by approximately 50% for up to one hour.

Oleic acid-13C is intended for use as an internal standard for the quantification of oleic acid by GC- or LC-MS. Oleic acid is a monounsaturated fatty acid and a major component of membrane phospholipids that has been found in human plasma, cell membranes, and adipose tissue.1,2 It contributes approximately 17% of the total fatty acids esterified to phosphatidylcholine, the major phospholipid class in porcine platelets.1 Oleic acid inhibits collagen-stimulated platelet aggregation by approximately 90% when used at a concentration of 10 μg/ml. It also inhibits fMLF-induced neutrophil aggregation and degranulation by 55 and 68%, respectively, when used at a concentration of 5 μM, similar to arachidonic acid .3 Oleic acid (60 μM) induces release of intracellular calcium in human platelets.4

Ingenol 3,20-dibenzoate is a powerful activator of protein kinase C (PKC) isoforms that effectively induces the translocation of nPKC-delta, -epsilon, and -theta, as well as PKC-mu, from the cytosolic fraction to the particulate fraction. Through de novo synthesis of macromolecules, it triggers apoptosis with characteristic morphology. Moreover, Ingenol 3,20-dibenzoate enhances IFN-γ production and degranulation in NK cells, particularly when stimulated by NSCLC cells[1][2].

PAR2 (1-6) amide is a synthetic peptide agonist of proteinase-activated receptor 2 (PAR2) that corresponds to residues 1-6 of the amino terminal tethered ligand sequence of human PAR2 and residues 37-42 of the full-length sequence.1It binds to NCTC 2544 cells expressing human PAR2 (Ki= 9.64 μM in a radioligand binding assay) and induces calcium mobilization in the same cells (EC50= 0.075 μM).2PAR2 (1-6) amide (100 μM) reduces colony formation of A549 lung cancer cells.1It induces superoxide production and degranulation in isolated human eosinophils when used at a concentration of 500 μM.3PAR2 (1-6) amide (5 μmol/kg) induces tear secretion in rats when used in combination with amastatin .4 1.Bohm, S.K., Kong, W., Bromme, D., et al.Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2Biochem. J.314(Pt 3)1009-1016(1996) 2.Kanke, T., Ishiwata, H., Kabeya, M., et al.Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2Br. J. Pharmacol.145(2)255-263(2005) 3.Miike, S., McWilliam, A.S., and Kita, H.Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2J. Immunol.167(11)6615-6622(2001) 4.Nishikawa, H., Kawai, K., Tanaka, M., et al.Protease-activated receptor-2 (PAR-2)-related peptides induce tear secretion in rats: Involvement of PAR-2 and non-PAR-2 mechanismsJ. Pharmacol. Exp. Ther.312(2)324-331(2005)

Streptochlorin is a bacterial metabolite originally isolated from Streptomyces sp. SF2583 that has diverse biological activities, including antiangiogenic, antiproliferative, and anti-allergic properties. It inhibits TNF-α-induced NF-κB transcriptional activity and decreases proliferation of human umbilical vein endothelial cells (HUVECs) when used at concentrations ranging from 5 to 20 μM. Streptochlorin (12 μg/ml) decreases viability of, as well as induces apoptosis and increases the production of reactive oxygen species (ROS) in, Hep3B human hepatocellular carcinoma cells. It does not induce cytotoxicity in RBL-2H3 mast cells at concentrations up to 100 μM. Streptochlorin prevents degranulation in antigen-stimulated mast cells, as well as inhibits Syk kinase and the Src family kinases LYN and Fyn and reduces the secretion of TNF-α and IL-4 induced by dinitrophenyl-human serum album (DNP-HSA) in RBL-2H3 mast cells. It also decreases swelling and reduces scratching behavior in a mouse model of allergic dermatitis induced by dinitrofluorobenzene (DNFB).

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg/ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g/animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

LTB4 dimethyl amide is a moderate inhibitor of LTB4-induced degranulation of human neutrophils (Ki = 130 nM) and lysozyme release from rat PMNL. LTB4 dimethyl amide appears to be an antagonist of the LTB4 receptor on guinea pig lung membranes.

5(S),15(S)-DiHETE is synthesized by 15-LO from 5(S)-HETE. It potentiates the degranulation of human PMNL in response to PAF, but not fMLP, calcium ionophore A23187, or LTB4. 5(S),15(S)-DiHETE is chemotactic for eosinophils with an ED50 value of 0.3 μM.

20-hydroxy LTB4 is a metabolite of LTB4 in human neutrophils. In human leukocytes, LTB4 is inactivated by the enzyme LTB4 20-hydroxylase. 20-hydroxy LTB4 is not only much less active (~5%) compared to LTB4 in causing degranulation of PMNL, but actually inhibits LTB4-induced degranulation of human neutrophils (Ki = 13.3 nM). However, 20-hydroxy LTB4 is as active as LTB4 in contracting parenchymal strips from guinea pig lung. 20-hydroxy LTB4 retains considerable ligand binding affinity at the BLT2 receptor, but does not appear to function as an agonist.

pNPS-DHA is an arylamide derivative of docosahexaenoyl ethanolamide that has anti-allergic activity.1It inhibits degranulation of RBL-2H3 mast cells (IC50= 15 μM).pNPS-DHA (1,000 mg/kg) inhibits IgE-dependent passive cutaneous anaphylaxis (PCA) in mice. 1.Kim, I.-H., Kanayama, Y., Nishiwaki, H., et al.Structure-activity relationships of fish oil derivatives with anti-allergic activity in vitro and in vivoJ. Med. Chem.62(21)9576-9592(2019)