phospholipase a2

Phospholipase A2 (PLA2) is an enzyme that hydrolyzes fatty acids present in the sn-2 position of phospholipids, and is closely related to lipid metabolism and immune function.

SecretedPhospholipaseA2-IIA, Human (EC 3.1.1.4), a member of the antimicrobial peptide family, functions by hydrolyzing phospholipids, thereby releasing lysophospholipids and fatty acids. It is particularly proficient at hydrolyzing bacterial membranes.

BMS493 is an inverse agonist of the pan-retinoic acid receptor (RAR) that inhibits retinoic acid-induced differentiation, enhances the interaction of nuclear co-inhibitors with RARs, attenuates RA signaling, potentiates TPP-induced toxicity, and inhibits the increase in phospholipase A2 activity.

PACOCF3 (Palmityltrifluoromethylketone) (Palmityltrifluoromet hylketone) is an inhibitor of Ca(2+)-independent phospholipase A2(PLA2) with an IC 50 of 3.8 μM. PACOCF3 alters Ca 2+ signaling in renal tubular cells [1] [2].

Fuzapladib (IS-741) (IS-741) is a phospholipase A2 inhibitor that can inhibits the expression of Mac-1, a cell adhesion molecule. Fuzapladib blocks activation of adhesion molecules (integrin) expressed on the inflammatory cell surface to prevent inflammatory cells from adhering to vascular endothelial cells and infiltrating tissue and to control exacerbation of pancreatitis.

Rhamnetin (beta-Rhamnocitrin), a quercetin derivative found in Coriandrum sativum, has antioxidant and anti-inflammatory activities. Rhamnetin inhibits secretory phospholipase A2.

Varespladib methyl (LY333013), a bioavailable prodrug of Varespladib, is a selective group II secretory phospholipase A2 inhibitor.

Dodecylphosphocholine (DPC) is a substrate-type inhibitor of pancreas phospholipase A2. Dodecylphosphocholine is a detergent.

ONO-RS-082 is a Ca2+-independent phospholipase A2 inhibitor.

Luffariellolide is a terpene compound obtained from the marine sponge Hyrtios communis. It is an inhibitor of human synoviocyte protein phospholipase A2 (HSF-PLA2) and a retinoic acid receptor (RAR) agonist. Luffariellolide inhibits hypoxia (1% O2)-induced HIF-1 activation and inhibits cell growth.

Lp-PLA2-IN-3 is a potent, orally bioactive lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, effectively inhibiting recombinant human [Lp-PLA2] with an IC50 value of 14 nM.

AACOCF3 (Arachidonyl trifluoromethyl ketone) is a cell-permeable trifluoromethyl ketone analog of arachidonic acid and a potent, selective slow binding inhibitor of the 85-kDa cytosolic phospholipase A2 (cPLA2). By blocking the production of arachidonate and 12-hydroxyeicosatetraenoic acid in calcium ionophore-challenged platelets, AACOCF3 hinders their synthesis. Additionally, AACOCF3 inhibits glucose-induced insulin secretion from isolated rat islets, making it promising for cardiovascular disease research.

Mepacrine (Erion) is an acridine derivative formerly widely used as an antimalarial. It is used in cell biological experiments as an inhibitor of phospholipase A2.

Pheniramine maleate (Trimetose), an alkylamine derivative with antihistaminic and vasodilatory properties, binds to histamine H1 receptors, thereby inhibiting phospholipase A2 and production of the endothelium-derived relaxing factor, nitric oxide.

Desonide (Prednacinolone) is a synthetic glucocorticosteroid for topical use, with anti-inflammatory activity. Desonide binds to glucocorticoid receptors in the cytoplasm, and the ligand-receptor complex is translocated as a homodimer into the nucleus, where transcription activation via glucocorticoid response elements within glucocorticoid-responsive genes occur. This agent induces transcription of genes coding for anti-inflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase. Increased synthesis of lipocortin-1 has an inhibitory effect on phospholipase A2, which in turn inhibits the release of arachidonic acid, thereby controlling the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

Clobetasol propionate (CGP9555) exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor-mediated gene expression. This results in the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Clobetasol Propionate is the propionate salt form of clobetasol, a topical synthetic corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2.

Tridecanoic acid (Tridecylic Acid) is a 13-carbon saturated fatty acid found in dairy products and also as a product of anaerobic biodegradation of n-hexadecane. It has been identified as a substrate of phospholipase A2.

Benzylideneacetone, a monoterpene produced by the insect pathogenic bacterium Xenorhabdus nematophila, is a phospholipase A2 (PLA2) inhibitor with inhibitory effects on arachidonoid biosynthesis and enhances baculovirus pathogenicity of Xylaria minor.

Triamcinolone (Aristocort) is a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. Upon cell entry, triamcinolone binds to and activates the glucocorticoid receptor, which leads to translocation of the ligand-receptor complex to the nucleus and induces expression of glucocorticoid-responsive genes such as lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both mediators of inflammation. In addition, pro-inflammatory cytokine production, including interleukin (IL)-1and IL-6, and the activation of cytotoxic T-lymphocytes is also inhibited. T-cells are prevented from making IL-2 and proliferating. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis through increasing Ikappa-B expression and curtailing activation of nuclear factor (NF)kappa-B.

1-Linoleoyl Glycerol (Monolinolein) is fatty acid glycerol that has been isolated from Saururus Chinensis roots. The (R)-1-Linoleoyl Glycerol and (S)-1-Linoleoyl Glycerol exhibit Lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitory activities with IC50 values of 45.0 and 52.0 μM, respectively.

Lp-PLA2-IN-2 is a selective and potent lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, with an IC50 of 120 nM for recombinant human Lp-PLA2.

sPLA2-X Inhibitor 31 is a selective inhibitor of secreted phospholipase A2 type X (sPLA2-X) with IC50 values of 26 nM for sPLA2-X, 310 nM for sPLA2-IIa, and 2230 nM for sPLA2-V.

Tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP) isolated from Vitex negundoL inhibits secretory phospholipase A2 (sPLA2). Tris(2,4-di-tert-butylphenyl)phosphate has anti-inflammatory activity.

2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide inhibits stress-induced ulcers by maintaining phospholipase A2 and prostaglandin E2 levels in rats subjected to water immersion-restrained stress-induced ulceration.