vascular permeability

PAF (C16) is a potent MAPK and MEK ERK activator that induces increased vascular permeability. PAF (C16) (PAF (C16)) is a platelet-activating factor, a phospholipid-derived mediator and a ligand for PAF G protein-coupled receptor (PAFR). PAF (C16) has shown anti-apoptotic and anti-inflammatory activity in vitro, inhibiting Caspase-dependent apoptosis by interacting with its receptor (PAF-R) to perform cell signaling.

Bromfenac sodium hydrate (Bromfenac monosodium salt sesquihydrate) is the sodium salt form of bromfenac, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties. Upon ophthalmic administration, bromfenac binds to and inhibits cyclooxygenase II (COX II), an enzyme that converts arachidonic acid to cyclic endoperoxides, which are prostaglandin (PG) precursors. By inhibiting PG formation, bromfenac prevents PG-induced inflammation, vasodilation, leukocytosis, disruption of the blood-aqueous humor barrier, increased vascular permeability, and elevated intraocular pressure (IOP).

Desloratadine (Sch34117) is a long-acting piperidine derivate with selective H1 antihistaminergic and non-sedating properties. Desloratadine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching and spasmodic contractions of gastrointestinal smooth muscle. Desloratadine is used to provide symptomatic relieve of allergic symptoms.

Emedastine (LY188695) is a second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.

Clorgyline (M&B 9302), an irreversible and selective MAO-A inhibitor with the advantages of oral activity and blood-brain barrier permeability, has an antidepressant effect by structurally altering the enzyme through the formation of intermediate radical cations, and reduces 1% fbs-stimulated VSMC (vascular smooth muscle cell) growth.

NS-2028 is a highly selective soluble Guanylyl Cyclase (sGC) inhibitor (IC50: 30 nM and 200 nM for basal and NO-stimulated enzyme activity) commonly used in nitric oxide signaling pathway research. It inhibits sGC activity in mouse cerebellum homogenates and neuronal NO synthase (IC50: 17 nM and 20 nM), inhibits 3-morpholino-sydnonimine (SIN-1)-elicited cyclic GMP formation in human cultured umbilical vein endothelial cells (IC50: 30 nM), and completely inhibits NO-dependent relaxant responses in non-vascular smooth muscle (1 μM). NS-2028 also decreases vascular endothelial growth factor-induced angiogenesis and permeability.

Diflapolin is a highly active dual 5-lipoxygenase-activating protein (FLAP) and soluble epoxide hydrolase (sEH) inhibitor, exhibiting marked anti-inflammatory efficacy and high target selectivity.

Emedastine Difumarate is a selective histamine H1 receptor antagonist with anti-allergic activity, prescribed for allergic conjunctivitis. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeabil

Tivozanib (KRN951) is an orally bioavailable inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 with potential antiangiogenic and antineoplastic activities.

Leukotriene F-4 sulfone induces vascular permeability changes.

14,15-Leukotriene D4 (14,15-LTD4) is a member of an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-lipoxygenases (15- and 12-LOs) on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. 14,15-LTD4 is classified as an eoxin (EXD4), because it is formed mostly by eosinophils. However, mast cells and nasal polyps can synthesize 14,15-LTD4 as well. Little is known about the physiological actions of 14,15-LTD4. It has weak contractile activity on both guinea pig ileum and pulmonary parenchyma in contrast to the effects of 5-LO-derived LTs. However, in an in vitro permeability assay, 14,15-LTD4 can increase vascular permeability of human endothelial cell monolayers, with similar potency to that of 5-LO-derived LTs, resulting in plasma leakage, a hallmark of inflammation.

Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes. The majority of these metabolites are formed through the 5-lipoxygenase (5-LO) pathway. 14,15-LTE4 is a metabolite of 14,15-LTC4 and 14,15-LTD4, an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-LOs on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. These metabolites are classified as eoxins because they are formed mostly by eosinophils. Mast cells and nasal polyps can synthesize 14,15-LTC4 as well, however metabolism to 14,15-LTE4 in these cells and tissue has not been documented. 14,15-LTE4 increases vascular permeability of human endothelial cell monolayers with about 10-fold less potency than LTC4, but approximately 100-fold greater potency than histamine.

Leukotriene C4 (LTC4) is the parent cysteinyl-leukotriene produced by the LTC4 synthase-catalyzed conjugation of glutathione to LTA4. LTC4 is produced by neutrophils, macrophages, and mast cells, and by transcellular metabolism in platelets. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4-induced bronchoconstriction and enhanced vascular permeability contribute to the pathogenesis of asthma and acute allergic hypersensitivity. The concentration of LTC4 required to produce marked contractions of lung parenchymal strips and isolated tracheal rings is about 1 nM. LTC4 methyl ester is a more lipid soluble form of LTC4. The biological activity of LTC4 methyl ester has not been reported.

SPHINX31 is a potent inhibitor of serine arginine-rich protein kinase 1 (SRPK1; IC50: 5.9 nM).

1. Yunaconitine (Guayewuanine B) has anti-inflammatory and analgesic actions. 2. Yunaconitine was shown to have anti-thermic effect in pyrexial rats when administered orally at a dose of 5 μg kg. 3. Yunaconitine shows positive effect in the granuloma inhibition test when it was subcutaneously injected, 1 μg kg for 6 d, or added directly to the cotton-pellet. 4. Yunaconitine inhibited the increased vascular permeability caused byacetic acid and histamine, the leucocyte migratory response induced by injection of 1 % carrageenin .1 ml in rat's thoracic cavity.

Halobetasol propionate (BMY-30056) is the propionate salt form of halobetasol, a synthetic corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictor activities. Halobetasol, a topical steroid, diffuses across cell membranes to interact with cytoplasmic corticosteroid receptors located in both the dermal and intradermal cells, thereby activating gene expression of anti-inflammatory proteins mediated via corticosteroid receptor response element. Specifically, this agent induces phospholipase A2 inhibitory proteins, which inhibit the release of arachidonic acid, thereby inhibiting the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes. As a result, halobetasol reduces edema, erythema, and pruritus through its cutaneous effects on vascular dilation and permeability.

EHT-6706 is a novel microtubule-disrupting agent that targets the colchicine-binding site to inhibit tubulin polymerization. At low nM concentrations, EHT 6706 exhibits highly potent antiproliferative activity on more than 60 human tumor cell lines, even those described as being drug resistant. EHT 6706 also shows strong efficacy as a vascular-disrupting agent, since it prevents endothelial cell tube formation and disrupts pre-established vessels, changes the permeability of endothelial cell monolayers and inhibits endothelial cell migration. Genome-wide transcriptomic analysis of EHT 6706 effects on human endothelial cells shows that the antiangiogenic activity elicits gene deregulations of antiangiogenic pathways. These findings indicate that EHT 6706 is a promising tubulin-binding compound with potentially broad clinical antitumor efficacy.

Angiogenesis inhibitor BT2 is a novel inhibitor of angiogenesis and vascular permeability, inhibiting ERK phosphorylation and the expression of FosB ΔFosB, VCAM-1, and many genes involved in proliferation, migration, angiogenesis, and inflammation, interacting with MEK1, suppressing retinal CD31, pERK, VCAM-1, and VEGF-A165 expression.

Abicipar pegol (AGN-150998, MP0112), an anti-VEGF DARPin molecule, is a novel class of small ankyrin repeat domain-containing proteins designed for high specificity and affinity targeting. This compound effectively inhibits angiogenesis and vascular permeability, and has been applied in ocular inflammation-related disease studies through intravitreal injections, significantly reducing mean retinal thickness and leakage area [1] [2].

Mirococept (APT070), an antibody designed to target the complement system components C3b C4b and act as a membrane-localizing C3 convertase inhibitor, effectively diminishes the release of C-peptide and pro-inflammatory cytokines. It also curtails the infiltration of inflammatory cells and intraislet inflammation, offering advantages for islet transplantation. Furthermore, Mirococept mitigates increased vascular permeability in intestinal and pulmonary contexts, thereby reducing neutrophil influx [1] [2].

C5a Receptor Agonist (mouse, human) is a bioactive peptide derived from the C-terminus of the complement fragment 5 anaphylatoxin (C5a), functioning as an agonist for the C5a receptor. This peptide plays a role in mediating inflammatory responses by promoting chemotaxis, leukocyte degranulation, enhanced vascular permeability, and cytokine production. Its agonistic activity is critically dependent on the presence of cyclohexylalanine at position 5 and the d-isomer of Arg at the terminal position.

1CAY10649, a thiazolinone compound, directly inhibits 5-lipoxygenase (5-LO) product formation in intact polymorphonuclear leukocytes (PMNL) with an IC50 value of 0.28 μM and in a soluble fraction of an S100 PMNL cell lysate with an IC50 value of 0.09 μM, following stimulation by calcium and arachidonic acid. This activity highlights its potential in mitigating inflammatory responses by targeting the biosynthesis of leukotrienes, substances implicated in various inflammatory processes such as neutrophil chemotaxis, increased vascular permeability, and smooth muscle contraction.

Leukotriene C4 (14,15-LTC4) is an inflammatory mediator synthesized from arachidonic acid through the actions of 15- and 12-lipoxygenases (LOs), involving intermediates such as 15-HpETE and 14,15-LTA4. Unlike the majority of leukotrienes formed via the 5-LO pathway, 14,15-LTC4 is an eoxin predominantly produced by eosinophils, although mast cells and nasal polyps can also synthesize it. While its physiological roles are not well understood, 14,15-LTC4 exhibits limited contractile activity on guinea pig ileum and pulmonary parenchyma. However, it can increase vascular permeability in human endothelial cell monolayers in vitro with potency comparable to 5-LO-derived leukotrienes, contributing to plasma leakage characteristic of inflammation.

Desloratadine-d5 is a deuterated compound of Desloratadine. Desloratadine has a CAS number of 100643-71-8. Desloratadine is a long-acting piperidine derivate with selective H1 antihistaminergic and non-sedating properties. Desloratadine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching and spasmodic contractions of gastrointestinal smooth muscle. Desloratadine is used to provide symptomatic relieve of allergic symptoms.