phospholipase

Phospholipase D (PLD), an enzyme within the phospholipase superfamily, is prevalent across bacteria, yeast, plants, animals, and viruses, serving roles in biochemical research. It catalyzes the hydrolysis of glycerophospholipids' phosphodiester bonds, generating phosphatidic acid and soluble choline. PLD is implicated in numerous disease-related pathways, such as diabetes, atherogenesis, obesity, tumorigenesis, immune responses, and neuroendocrine functions [1].

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).

GW4869 (GW69A) is a selective and non-competitive inhibitor of neutral sphingomyelinase N-SMase (IC50=1 μM). GW4869 also inhibits exosome synthesis/release and is commonly used in exosome-related studies.

Neomycin sulfate (Framycin sulfate) is a broad-spectrum aminoglycoside antibiotic that blocks the synthesis of bacterial proteins in order to exert antimicrobial activity. Neomycin sulfate is commonly used to screen prokaryotic and eukaryotic cells for Neo resistance genes.

1. Glaucocalyxin A (Leukamenin F)-SBE-β-CD could be useful with a better solubility and sustained function in drug delivery. 2. Glaucocalyxin A activates caspase-3, decreases BAD phosphorylation, and reduces the expression of X-linked inhibitor of apoptosis protein. 3. Glaucocalyxin A inhibits Akt phosphorylation, suppresses proliferation, and promotes apoptosis in a dose-dependent manner, but not in normal glial cells. 4. Glaucocalyxin A inhibits collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. 5. Glaucocalyxin A could potentially be developed as an antiplatelet and antithrombotic agent, can inhibit platelet p-selectin secretion and integrin activation by convulxin, is a GPVI selective ligand.

Amentoflavone (3',8''-Biapigenin), as a potent inhibitor of CYP3A4 and CYP2C9, can interact with many other medications. CYP3A4 and CYP2C9 are proteins used for drug metabolism in the body. Amentoflavone also is an inhibitor of human cathepsin B. It has antimalarial activity in trials significant affinities towards the Delta-1, kappa opioid receptors (as an antagonist) and binds to benzodiazepine receptors. Amentoflavone may be a potential lead for a new type of anti-inflammatory agents having the dual inhibitory activity of group II phospholipase A2 and cyclooxygenase. Amentoflavone and quercetin differentially exerted suppression of PGE2 biosynthesis via downregulation of COX-2/iNOS expression.

CCR1/5/8 activator 1 is a cytoplasmic phospholipase A inhibitor with antifungal activity.

Hnps-PLA Inhibitor is an inhibitor of human nonpancreatic secretory Phospholipase A (hnps-PLA).

VU 0364739 hydrochloride (VU 0364739 HCl) is a selective and potent inhibitor of phospholipase D2 (PLD2) with IC50s of 20 and 1500 nM for PLD2 and PLD1, respectively.VU 0364739 hydrochloride exhibits potential anticancer activity and induces apoptosis. VU 0364739 hydrochloride has potential anticancer activity, induces apoptosis, and can be used in the study of cancer and metabolic-related diseases.

VU0285655-1(BML-280) is a potent and selective phospholipase D2 (PLD2) inhibitor that inhibits the proliferation of PLD2-deficient cells.VU0285655-1 has an inhibitory effect on high glucose-induced caspase-3 cleavage and reduction of cell viability.VU0285655-1 is used in the study of diabetic retinopathy.

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.

Linocinnamarin (3-[4-(beta-D-Glucopyranosyloxy)phenyl]acrylic acid methyl ester) is isolated from Fragaria ananassa Duch. (strawberry). The inhibition of antigen-stimulated degranulation by LN is mainly due to inactivation of Syk/phospholipase Cgamma (PLCgamma) pathways.

CGP 35949 is an LTD4 antagonist with phospholipase inhibitory activity.

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).

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.

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

Halopemide is a potent inhibitor of PLD (IC50 = 220 and 310 nM for human PLD1 and PLD2). Halopemid is an antagonist of dopamine receptors. Halopemid can be used in psychotropic research.

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.

ML299 (VU0463568) is a dual PLD1/2 inhibitor (PLD1 and PLD2, IC50 of 6 nM, 20 nM, respectively).

VU0359595 (ML-270) is a potent and selective pharmacological phospholipase D1 (PLD1) inhibitor with an IC50 of 3.7 nM. VU0359595 is >1700-fold selective for PLD1 over PLD2 (IC50 of 6.4 μM). VU0359595 can be used for the research of cancer, diabetes, neurodegenerative and inflammatory diseases.

AACOCF3 (Arachidonyl trifluoromethyl ketone) is a cell-permeable trifluoromethyl ketone analog of arachidonic acid. It is a potent and 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. Moreover, AACOCF3 inhibits glucose-induced insulin secretion from isolated rat islets. Given its diverse applications, AACOCF3 holds promise for cardiovascular disease research.

Ecopladib (PLA 725) is a sub-micromolar inhibitor of cytosolic phospholipase A2α (cPLA2α), with IC50s of 0.15 μM and 0.11 μM in the GLU micelle and rat whole blood assays, respectively.

Vinaxanthone (SM-345431) is a small molecule compound derived from Penicillium chrysogenum that is a selective and potent semaphorin3A, phospholipase C (PLC), and FabI inhibitor, inhibiting semaphorin3A and FabI.Vinaxanthone exhibits antimicrobial activity, blocking intracellular fatty acid synthesis and inhibiting the growth of Staphylococcus aureus.

inhibits phosphatidylinositol phospholipase C

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.

FIPI (5-Fluoro-2-indolyl deschlorohalopemide) is a derivative of halopemide which potently inhibits both PLD1 (IC50 = 25 nM) and PLD2 (IC50 = 20 nM); prevents PLD regulation of F-actin cytoskeleton reorganization, cell spreading, and chemotaxis.

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

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

U-73343 is an inactive analog of U-73122 and can be used as a negative control. It dose-dependently inhibits acid secretion irrespective of the stimulant. It is a phospholipase C (PLC) and 5-LO (5-lipoxygenase) inhibitor with an IC50 of 1-2.1 μM for PLC.

Lansoprazole (A-65006) is a 2, 2, 2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)

BAPTA is a neuroprotective agent in cerebral ischemia, acting as an intercellular Ca2+ chelator.

CAY10594 is a potent phospholipase D2(PLD2) inhibitor. CAY10594 ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis.

ML348 (GNF-Pf-1127) is a selective and reversible lysophospholipase 1 (LYPLA1) inhibitor (IC50 = 210 nM).

Omeprazole (Losec) is a proton pump inhibitor (PPI), Omeprazole(Losec) is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor).

A4333, a biotinylated derivative of A3373, selectively inhibits Phospholipase D1 (PLD1) while sparing PLD2. It is noted for its significant role in antitumor activity [1].

LEI110 is a potent Phospholipase A2, group XVI (PLA2G16) inhibitor with an Ki value of 20 nM. LEI110 is a selective pan-inhibitor of the HRASLS family of thiol hydrolases (i.e., PLA2G16, HRASLS2, RARRES3 and iNAT).

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.

Dioleoylphosphatidylglycerol (DOPG), a naturally occurring phospholipid, is synthesized through the action of aquaporin 3 (AQP3) and phospholipase D2 (PLD2). It functions to suppress the production of inflammatory mediators by macrophages triggered by the activation of toll-like receptor 2 (TLR2) by heat shock protein B4 (HSPB4) [1].

WH-15 is a fluorogenic phospholipase C (PLC) reporter, exhibiting Michaelis-Menten constant (Km) values of 49, 30, and 86.1 µM for PLC-γ1, PLC-δ1, and PLC-β2, respectively. It undergoes enzymatic cleavage in a cascade reaction to produce fluorescent 6-aminoquinoline. This compound enables the imaging of PLC activity in live cells [1].

The phosphatidylinositol phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Centuarin α and the Akt-family of GTPase activating proteins are examples of PtdIns-(3,4,5)-P3-binding proteins. Protein-binding to PtdIns-(3,4,5)-P3 is important for cytoskeletal rearrangements and membrane trafficking. PtdIns-(3,4,5)-P3 is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. For further reading on inositol phospholipids, see also references and .

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.

Endogenous peptide GPR83 agonist. ProSAAS-derived neuropeptide. Activates phospholipase C (PLC)-mediated signaling cascade in mouse hypothalamus.

SR 142948A is a non-peptide antagonist of neurotensin receptor. SR 142948A affects the expression of c-Fos and has properties of antipsychotic agent. SR 142948A blocks hypothermia and analgesia induced by neurotensin. It blocks the increase in the concent

2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide is a compound known to inhibit stress-induced ulcers, effectively maintaining the levels of phospholipase A2 and prostaglandin E2 in rats subjected to water immersion-restrained stress-induced ulceration.

Mastoparan X, a tetradecapeptide derived from wasp venom, functions as a GTP-binding regulatory protein (G protein)-activating peptide. It directly activates G proteins coupled to phospholipase C, inducing secretion in various cell types [1].

Inostamycin A is a bacterial metabolite that has been found inStreptomycesand has anticancer activity.1It is an inhibitor of CDP-diacylglycerol:inositol 3-phosphatidyltransferase (IC50= 0.02 μg/ml in A431 cell membranes) and is selective for CDP-diacylglycerol:inositol 3-phosphatidyltransferase over phospholipase C (PLC) and phosphatidylinositol kinase at 10 μg/ml.2Inostamycin A decreases viability of YCU-T892, KCC-TC873, KB, HSC-4, and YCU-T891 oral squamous cell carcinoma (OSCC) cells in a concentration-dependent manner.3It induces cell cycle arrest in the G1phase in HSC-4 cells when used at a concentration of 250 ng/ml and induces apoptosis in Ms-1 small cell lung cancer cells at 300 ng/ml.3,4Inostamycin A also reduces levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 and inhibits EGF-induced migration of HSC-4 cells.5 1.Imoto, M., Umezawa, K., Takahashi, Y., et al.Isolation and structure determination of inostamycin, a novel inhibitor of phosphatidylinositol turnoverJ. Nat. Prod.53(4)825-829(1990) 2.Imoto, M., Taniguchi, Y., and Umezawa, K.Inhibition of CDP-DG: inositol transferase by inostamycinJ. Biochem.112(2)299-302(1992) 3.Baba, Y., Tsukuda, M., Mochimatsu, I., et al.Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell carcinoma cell linesCell Biol. Int.25(7)613-620(2001) 4.Imoto, M., Tanabe, K., Simizu, S., et al.Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cellsJpn. J. Cancer Res.89(3)315-322(1998) 5.Baba, Y., Tsukuda, M., Mochimatsu, I., et al.Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): Inositol transferase, suppresses invasion ability by reducing productions of matrix metalloproteinase-2 and -9 and cell motility in HSC-4 tongue carcinoma cell lineClin. Exp. Metastasis18(3)273-279(2000)