pla2

Lp-PLA2-IN-2 is a selective and potent lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, with an IC50 0f 120 nM for recombinant human Lp-PLA2.

Lp-PLA2-IN-3 is a potent and orally bioactive lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor that inhibits recombinant human Lp-PLA2 with an IC50 value of 14 nM.

Lp-PLA2-IN-14 (Compound 19), an inhibitor of rhLp-PLA2, exhibits a potent inhibitory effect with a pIC50 value of 8.4. This compound is applicable in research pertaining to neurodegenerative disorders, including Alzheimer Disease (AD), glaucoma, age-related macular degeneration (AMD), and cardiovascular diseases such as atherosclerosis [1].

Lp-PLA2-IN-15 (example 2) is an inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with potential application in Alzheimer's disease research [1].

Lp-PLA2-IN-10 is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as platelet-activating factor acetylhydrolase (PAF-AH). This enzyme plays a role in the hydrolysis of lipoprotein lipids or phospholipids. The compound holds research potential for neurodegenerative diseases such as Alzheimer's disease (AD), as well as glaucoma, age-related macular degeneration (AMD), and cardiovascular diseases like atherosclerosis[1].

Lp-PLA2-IN-9 (compound 17) is a tetracyclic pyrimidinone compound, a potent inhibitor of Lp-PLA2 that acts on rhLp-PLA2 (pIC50: 10.1). lp-PLA2-IN-9 has shown research potential in neurodegenerative diseases.

Lp-PLA2-IN-13 (compound 15), a potent Lp-PLA2 inhibitor, holds potential for research in neurodegenerative-related diseases [1].

Lp-PLA2-IN-16 (Example 1) is an inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with potential applications in Alzheimer's disease research [1].

Lp-PLA2-IN-5 is a potent lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2-IN-5 has the potential to be studied in diseases associated with Lp-PLA2 activity, such as Alzheimer's disease, atherosclerosis.Lp-PLA2-IN-5 is an inhibitor of platelet-activating factor acetylhydrolase (PAF-AH), a phospholipase A2 involved in lipoprotein lipid or phospholipid hydrolysis. Compound 35).

Lp-PLA2-IN-11 is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2-IN-11 has the potential to be investigated in diseases associated with Lp-PLA2 activity (e.g. atherosclerosis, Alzheimer's disease).

Lp-PLA2-IN-4 is a potent lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2-IN-4 has the potential to be studied in diseases associated with Lp-PLA2 activity, such as Alzheimer's disease, atherosclerosis, and is an inhibitor of platelet-activating factor acetylhydrolase (PAF-AH), a phospholipase A2 involved in lipoprotein lipid or phospholipid hydrolysis. Compound 38).

Lp-PLA2-IN-1 (Lp-PLA2 inhibitor 1) suppresses Lp-PLA2 activity processes for their preparation. Lp-PLA2-IN-1 (Lp-PLA2 inhibitor 1) also inhibits to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example, atherosclerosis, Alzheimer's disease.

Lp-PLA2-IN-12 (compound 19), an Lp-PLA2 inhibitor, is utilized in researching neurodegenerative diseases including Alzheimer's disease (AD), glaucoma, age-related macular degeneration (AMD), and cardiovascular conditions such as atherosclerosis [1].

Lp-PLA2-IN-6 is a tetracyclic pyrimidinone compound that is a potent inhibitor of Lp-PLA2 and is able to act on rhLp-PLA2 (pIC50: 10.0). lp-PLA2-IN-6 has shown research potential in neurodegenerative diseases.

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.

Darapladib (SB-480848)(IC50=0.25 nM) is a substituted pyrimidone with inhibitory activity towards lipoprotein-associated phospholipase-A2 (Lp-PLA2).

The sPLA2-IIA Inhibitor is a cyclic pentapeptide analog of FLSYK, specifically cyclic 2-Nal-Leu-Ser-2-Nal-Arg (c2), which interacts with human IIA phospholipase A2 (hGIIA) to impede its ester bond hydrolyzing function. As part of the esterase superfamily, sPLA2 enzymatically cleaves the sn-2 ester bond in glycerophospholipids, releasing arachidonic acid and lysophospholipids[1].

FAAH/cPLA2α-IN-1 is a compound that simultaneously inhibits both FAAH and cPLA2α, demonstrating potent activity with half-maximal inhibitory concentrations (IC50s) of 32 nM for FAAH and 47 nM for cPLA2α [1].

Melittin Acetate (Forapin Acetate) is a PLA2 activator. Melittin Acetate stimulates the activity of the low molecular weight PLA2, while it does not increase the activity of the high molecular weight PLA2.

Melittin TFA is a small protein containing 26 amino acid residues, is the principal toxic component of bee venom. Melittin is a PLA2 activator, stimulates the activity of the low molecular weight PLA2, while it does not the increase activity of the high m

9-Oxononanoic Acid is an oxidized fatty acid, formed by the autoxidation of linoleic acid, which enhances phospholipase A2 (PLA2) activity and increases the production of thromboxane B2 in isolated human plasma.9-Oxononanoic Acid reduces hepatic neofatty acid synthesis and enhances the activity of rat hepatic carnitine palmitoyltransferase, a marker of β-oxidation. Activity.

Anti-Inflammatory Peptide 1 Acetate (C45H82N12O14S2) possesses a potent anti-inflammatory activity in vivo and is a strong inhibitor of phospholipase A2 (PLA2), whose increased presence and activity results in inflammation and pain at certain bodily sites

Darapladib-impurity is the impurity of Darapladib. Darapladib inhibits lipoprotein-associated phospholipase A2 (Lp-PLA2).

sPLA2-X Inhibitor 31 is a selective inhibitor of secreted phospholipase A2 type X (sPLA2-X) (IC50s of 26 nM, 310 nM, and 2230 nM for sPLA2-X, sPLA2-IIa, and sPLA2-V, respectively).

KH064 is a sPLA2-IIA inhibitor of oral activity.

Varespladib (LY315920), a specific and effective human non-pancreatic secretory phospholipase A2 (hnsPLA) inhibitor(IC50=7 nM), has been investigated for the treatment and prevention of sickle cell disease, vaso-occlusive crisis, and acute coronary syndrome.

N-(p-amylcinnamoyl) Anthranilic Acid (ACA) is a broad spectrum Phospholipase A2 (PLA2) inhibitor and TRP channel blocker.

C22 Glucosylceramide (d18:1/22:0) is an endogenous glucosylceramide. Glucosylceramides are major constituents of skin lipid membranes where they play a role in maintaining the water permeability barrier. They are precursors in the synthesis of lactosylceramide , as well as oligoglycolipids and gangliosides. Phospholipase A2 (PLA2) type XIIA knockdown increases C22 glucosylceramide (d18:1/22:0) expression in rat brain. It is also increased in the brain, but not the liver or spinal cord, of mice fed a methionine-restricted diet. In human athletes, plasma levels of C22 glucosylceramide (d18:1/22:0) increase during exercise and return to basal levels during recovery. This product contains C22 glucosylceramide (d18:1/22:0) isolated from bovine buttermilk.

Phosphatidylethanolamines are important components of cell membranes and biochemical pathways of fatty acid synthesis. 1-Palmitoyl-2-linoleoyl PE (PLPE) is one of the many phosphatidylethanolamines that may be present in cellular membranes. It has been used in studies involving the biosynthesis of anandamide via the phospholipase A2 (PLA2) and lysoPLD pathways. PLPE can also be used as a specific substrate to assess the activity of sPLA2-IIA in the presence of other phospholipids.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA2α with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and the production of PGE2, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.

Thioester analogs of glycerophospholipids, in combination with Ellman's reagent, are convenient colorimetric substrates for the measurement of phospholipase (PL) activity. Palmitoyl thio-PC is a chromogenic PLA2 substrate that contains a palmitoyl thioester at the sn-2 position of the glycerol backbone. Hydrolysis of the thioester by PLA2 yields a free thiol that reacts readily with DTNB (Ellman's reagent) giving a bright yellow product with an absorbance maximum at 412 nm. Palmitoyl thio-PC has been used to measure bee venom sPLA2 activity in a phospholipid:Triton X-100 mixed micelle system.

Plipastatin A1, a lipopeptide isolated from B. cereus, demonstrates enzyme inhibitory and immunosuppressant properties. It effectively inhibits enzymes phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD) with half-maximal inhibitory concentrations (IC50s) of 2.9, 1.3, and 1.4 µM, respectively. Additionally, at a concentration of 100 µg/ml, plipastatin A1 inhibits lipopolysaccharide (LPS)-induced B cell blastogenesis and T cell blastogenesis triggered by concanavalin A. In vivo studies reveal that a dose of 0.1 mg/animal effectively suppresses delayed-type hypersensitivity in mice.

SB-435495 is an orally active, selective and potent Lp-PLA2 inhibitor (IC50: 0.06 nM) for the study of autoimmune uveitis and atherosclerosis.

SB-435495 ditartrate is a potent, selective, reversible, non-covalent, and orally active inhibitor of Lp-PLA2, demonstrating an IC50 value of 0.06 nM [1] [3].

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.

Luffariellolide is an inhibitor of human synovial fluid phospholipase A2 ( HSF-PLA2 ) (IC 50 =5 μM). PMA-induced ear edema was effectively inhibited by luffariellolide (ED 50 =50 μg/ear) [1].

Fludrocortisone acetate (9α-Fludrocortisone acetate) , a glucocorticoid-receptor agonist, binds to cytoplasmic receptors, translocates to the nucleus, and subsequently initiates the transcription of glucocorticoid-responsive genes such as lipocortins to inhibit phospholipase A2 (PLA2). Fludrocortisone acetate is the acetate salt of a synthetic fluorinated corticosteroid with anti-inflammatory and antiallergic activities. Inhibition of PLA2 activity prevents the release of arachidonic acid, a precursor of eicosanoids such as prostaglandins and leukotrienes; eicosanoids are important mediators in the pro-inflammatory response mechanism. As a mineralocorticoid-receptor agonist, this agent stimulates Na+ reabsorption and water retention and K+ and H+ secretion in the distal tubules and collecting ducts of the kidney.

1. Columbin has anti-inflammatory activity. 2. Columbin has chemopreventive ability against human colon cancer. 3. Columbin inhibits PLA2 hydrolysis of ghost RBC in a dose-dependent fashion.

trans-Benzylideneacetone (Acetocinnamone) is used in various synthetic preparations.

Arachidonoyl Thio-PC is a substrate for many phospholipase A2s (PLA2s) including sPLA2, cPLA2, and iPLA2. Cleavage of the sn-2 fatty acid by PLA2 results in generation of a free thiol which reacts with chromogenic reagents such as DTNB (Ellman's reagent) and DTP to allow quantitation of PLA2 activity. Isozyme-specific cPLA2 activity can be measured by excluding or inhibiting sPLA2 and iPLA2 activities in the assay.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes. AX 048 is a potent group IVA cPLA2 inhibitor that demonstrates 50% inhibition of the enzyme at a mole fraction (XI(50)) of 0.022. Pretreatment with AX 048 (ED50 = 1.2 mg/kg) dose-dependently reduces thermal hyperalgesia evoked by carrageenan injection of rat hind paw. At concentrations as high as 30 μM, AX 048 does not inhibit COX activity or interfere with central cannabinoid receptor signaling.

Bromoenol lactone is a suicide-based irreversible, selective, potent inhibitor of calcium-independent phospholipase A2 (iPLA2β; IC50: ~7 μM). It inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx.

Elaidamide is a fatty acid amide that has been found in the cerebrospinal fluid of sleep-deprived cats.1 It inhibits rat microsomal epoxide hydrolase (mEH; Ki = 70 nM).2 Elaidamide also inhibits porcine pancreatic and human synovial phospholipase A2 (PLA2).3 In vivo, elaidamide (10 mg/animal) induces physiological sleep in rats.1References1. Cravatt, B.F., Prospero-Garcia, O., Siuzdak, G., et al. Chemical characterization of a family of brain lipids that induce sleep. Science 268(5216), 1506-1509 (1995).2. Morisseau, C., Newman, J.W., Dowdy, D.L., et al. Inhibition of microsomal epoxide hydrolases by ureas, amides, and amines. Chem. Res. Toxicol. 14(4), 409-415 (2001).3. Jain, M.K., Ghomashchi, F., Yu, B.Z., et al. Fatty acid amides: scooting mode-based discovery of tight-binding competitive inhibitors of secreted phospholipases A2. J. Med. Chem. 35(19), 3584-3586 (1992). Elaidamide is a fatty acid amide that has been found in the cerebrospinal fluid of sleep-deprived cats.1 It inhibits rat microsomal epoxide hydrolase (mEH; Ki = 70 nM).2 Elaidamide also inhibits porcine pancreatic and human synovial phospholipase A2 (PLA2).3 In vivo, elaidamide (10 mg/animal) induces physiological sleep in rats.1 References1. Cravatt, B.F., Prospero-Garcia, O., Siuzdak, G., et al. Chemical characterization of a family of brain lipids that induce sleep. Science 268(5216), 1506-1509 (1995).2. Morisseau, C., Newman, J.W., Dowdy, D.L., et al. Inhibition of microsomal epoxide hydrolases by ureas, amides, and amines. Chem. Res. Toxicol. 14(4), 409-415 (2001).3. Jain, M.K., Ghomashchi, F., Yu, B.Z., et al. Fatty acid amides: scooting mode-based discovery of tight-binding competitive inhibitors of secreted phospholipases A2. J. Med. Chem. 35(19), 3584-3586 (1992).

OBAA is a potent inhibitor of phospholipase A2 (PLA2) with an IC 50 of 70 nM. OBAA blocks Melittin-induced Ca 2+ influx in Trypanosoma brucei with an IC 50 of 0.4 μM [1] [2] [3].

Melittin free acid, a basic 26-amino-acid polypeptide, constitutes the primary active component of honeybee venom and serves as a phospholipase A2 (PLA2) activator. Exhibiting a broad-spectrum antifungal effect, it presents MIC values ranging from 0.4-60 μM. Its mechanism includes inducing cell apoptosis, inhibiting (1,3)-β-D-glucan synthase, and engaging in multiple pathways [1] [2].

Rapanone (2,5-Dihydroxy-3-tridecyl-[1,4]benzoquinone) is a natural benzoquinone that is a potent and selective inhibitor of human synovial PLA2.

The phospholipases are an extensive family of lipid hydrolases that function in cell signaling, digestion, membrane remodeling, and as venom components. The calcium-independent phospholipases (iPLA2) are a PLA2 subfamily closely associated with the release of arachidonic acid in response to physiologic stimuli. (R)-Bromoenol lactone ((R)-BEL) is an irreversible, chiral, mechanism-based inhibitor of calcium-independent phospholipase γ (iPLA2γ). Unlike (S)-BEL, (R)-BEL does not inhibit iPLA2β except at high doses of 20-30 μM. (R)-BEL inhibits human recombinant iPLA2γ with an IC50 of approximately 0.6 μM.

Manoalide, a sesterterpenoid compound, serves as a potent inhibitor of Phospholipase A2 (PLA2) and Phospholipase C (PLC). It exhibits anti-inflammatory and antibacterial properties.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids at the sn-2 position leading to the production of lysophospholipids and free fatty acids. Calcium-dependent cytosolic PLA2 (cPLA2α) is a 85 kDa enzyme that plays a key role in the arachidonic cascade and the inflammatory response associated with this metabolic pathway. CAY10502 is a potent inhibitor of calcium-dependent cytosolic PLA2α (cPLA2α) with an IC50 value of 4.3 nM for the purified enzyme from human platelets. It inhibits arachidonic acid mobilization from A23187-stimulated or TPA-stimulated human platelets with IC50 values of 570 and 0.9 nM, respectively.

Rilapladib (SB 659032) is a selective inhibitor of Lipoprotein-Associated Phospholipase A2(Lp-PLA2, IC50 = 230 pM) and an antagonist of the platelet activating factor receptor.