phospholipase a-2

PACOCF3 (Palmityltrifluoromet​hylketone) (Palmityltrifluoromethylketone) 是一种钙非依赖性的磷脂酶 A2 (phospholipase A2) 抑制剂，IC50为 3.8 μM。PACOCF3 改变肾小管细胞中的 Ca2+信号传导。

Phospholipase A2 (PLA2) 是一种可水解存在于磷脂 sn-2 位置的脂肪酸的酶，与脂代谢和免疫功能密切相关。

Rhamnetin (beta-Rhamnocitrin) 是一种槲皮素衍生物，在芫荽中被发现，具有抗氧化和抗炎活性。Rhamnetin 可抑制分泌型磷脂酶 A2。

Dodecylphosphocholine (DPC) 是一种去污剂，普遍用于膜蛋白核磁共振的研究。

Amentoflavone (3',8''-Biapigenin) 是一种具有很多生物活性的双黄酮类天然产物，有抗炎、抗氧化和神经保护等作用。

Glaucocalyxin A (Leukamenin F) 是来自日本黑纹病菌的一种对映型月桂基二萜，具有抗肿瘤作用。它通过调节PI3K Akt 信号通路抑制 GLI1 的核易位，诱导骨肉瘤凋亡。

Triamcinolone (Aristocort) 是一种皮质类固醇激素受体激动剂，也是一种合成的长效糖皮质激素，具有抗炎活性。

3-Nitrocoumarin (3-nitrochromen-2-one) (3-NC) 是一个有效的、磷脂酶 C-γ (PLC-γ) 的选择性抑制剂。

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.

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.

2-Methylbutyrylcarnitine (chloride) 作为一种支链酰基肉碱，是肠道微生物代谢的产物。它通过结合血小板中的整合素α2β1，不仅促进细胞质磷脂酶 A2 (cPLA2) 的活化，而且增强了血小板的过度反应性。此外，实验表明，2-Methylbutyrylcarnitine (chloride) 能显著提升小鼠血小板的超反应性和血栓形成能力。

GK241 (compound 31a-c) 为一种2-氧代酰胺衍生的化学物质，展现了对人类与小鼠的IIA组分泌型磷脂酶A2（GIIA sPLA2）具有显著的抑制作用（IC50为143 nM与68 nM），其抑制机制已通过分子动力学模拟得到探讨。

OBAA 是一种有效的磷脂酶 A2 (PLA2) 抑制剂(IC50= 70 nM)，并且在布氏锥虫中阻断 Melittin 诱导的 Ca2+流入(IC50= 0.4 μM)。

Abroquinone A, a natural isoflavanquinone, has been shown to block cytosolic phospholipase A(2) and 5-lipoxygenase activation in neutrophils, it may have pharmaceutical potential as an antiallergic agent.

12-HETE ((±)12-HETE) 是 PGE2 的调节因子，具有抗血栓形成和促血栓形成作用，通过蛇毒 IIA 组磷脂酶 A2 诱导诱导 PGE2 释放和 COX-2 表达。12-HETE 还是一种神经调节剂，通过激活 NADPH 氧化酶和随后的生成激活视网膜细胞，诱导糖尿病视网膜病变的内皮功能障碍。

PGBx is a mixture of oligomers of PGB1 with a molecular weight of 1,000-1,500. It has antioxidant and free radical trapping activity that was first studied in isolated mitochondria.1 PGBx has anti-inflammatory and cytoprotective activity which may be attributed to inhibition of the 14 kDa sPLA2.2,3 At a dose of 1 mg/kg, PGBx significantly reduces the incidence of ulcers in rats.2References1. Polis, B.D., Polis, E., and Kwong, S. Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBΧ). Proceedings of the National Academy of Sciences of the United States of America 76, 1598-1602 (1979).2. Kumashiro, R., Devlin, T.M., Kholoussy, A.M., et al. Prostaglandin BΧ in the prevention of stress ulcers in rats. International Surgery 70, 247-250 (1985).3. Franson, R.C., Rosenthal, M.D., and Regelson, W. Mechanism(s) of cytoprotective and anti-inflammatory activity of PGB1 oligomers: PGBx has potent anti-phospholipase A2 and anti-oxidant activity. Prostaglandins, Leukotrienes and Essential Fatty Acids 43, 63-70 (1991). PGBx is a mixture of oligomers of PGB1 with a molecular weight of 1,000-1,500. It has antioxidant and free radical trapping activity that was first studied in isolated mitochondria.1 PGBx has anti-inflammatory and cytoprotective activity which may be attributed to inhibition of the 14 kDa sPLA2.2,3 At a dose of 1 mg/kg, PGBx significantly reduces the incidence of ulcers in rats.2 References1. Polis, B.D., Polis, E., and Kwong, S. Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBΧ). Proceedings of the National Academy of Sciences of the United States of America 76, 1598-1602 (1979).2. Kumashiro, R., Devlin, T.M., Kholoussy, A.M., et al. Prostaglandin BΧ in the prevention of stress ulcers in rats. International Surgery 70, 247-250 (1985).3. Franson, R.C., Rosenthal, M.D., and Regelson, W. Mechanism(s) of cytoprotective and anti-inflammatory activity of PGB1 oligomers: PGBx has potent anti-phospholipase A2 and anti-oxidant activity. Prostaglandins, Leukotrienes and Essential Fatty Acids 43, 63-70 (1991).

C2 Phytoceramide is a bioactive semisynthetic sphingolipid that inhibits formyl peptide-induced oxidant release (IC50 = 0.38 μM) in suspended polymorphonuclear cells. It increases COX-2 protein levels 15-fold through ERK signaling. It induces death of keratinocytes (20% viability) with an ED50 value of 30 μM, the same concentration at which 35% of cells in a TUNEL assay are apoptotic. C2 Phytoceramide also has antiproliferative effects in CHO cells, with greater than 80% cytotoxicity achieved at a concentration of 20 μM, and induces internucleosomal DNA fragmentation. In addition, it inhibits the activation of phospholipase D (PLD) mediated by muscarinic acetylcholine receptors in vitro.

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) containing C8:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacyl glycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog, compared to naturally-occurring PtdIns, gives it different physical properties including high solubility in aqueous media. PtdIns are phosphorylated to mono- (PtdIns-P; PIP), di- (PtdIns-P2; PIP2), and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.

The phosphatidylinositol (PtdIns) 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, also known as PIP3, 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. PIP3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking. PtdIns-(3,4,5)-P3 (1,2-dihexanoyl) is a synthetic analog of natural PIP3 with C6:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacylglycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog give it different physical properties from naturally-occurring PIP3, including higher solubility in aqueous media.

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(4)-P1 (1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) featuring C8:0 fatty acids at the sn-1 and sn-2 positions. The compound contains the same inositol and diacylglycerol (DAG) stereochemistry as the natural compound. PtdIns-(4)-P1 can be phosphorylated to di- (PtdIns-P2; PIP2) and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.

Tetranactin is a macrotetrolide and a monovalent cation ionophore that has been found in S. aureus and has antibacterial, insecticidal, and mitogenic activities. It exhibits an equilibrium permeability ratio 1,000-fold greater for lithium than sodium or cesium ions accross bilayer membranes at low voltages. Tetranactin inhibits the growth of Gram-positive bacteria and C. miyabeanus and R. solani fungi when used at concentrations less than 0.9 μg/ml. Tetranactin (0.5-1.5 μg per insect) dose-dependently increases the mortality of adult C. chinensis weevils up to 100% and has mitogenic activity against T. telarius when sprayed onto plants with an LC50 value of 9.2 μg/ml. It reduces IL-1β- and cAMP-induced secretion of phospholipase A2 (PLA2) from rat mesangial cells (IC50s = 43 and 33 nM, respectively). Tetranactin (50 ng/ml) suppresses the proliferation of human T lymphocytes induced by allogeneic cells and IL-2 and supresses the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures. In vivo, tetranactin (10 mg/animal per day) completely inhibits the formation of experimental autoimmune uveoretinitis (EAU) in rats.

Diheptanoyl Thio-PC is a substrate for all phospholipase A2s (PLA2s) with the exception of cPLA2 and PAF-acetyl hydrolase (PAF-AH). Interaction of this compound with a PLA2 results in cleavage of the sn-2 fatty acid generating a free thiol on the lysophospholipid. This free thiol can be detected using chromogenic substrates such as DTNB (Ellman's reagent) and DTP.

Phosphatidylcholine (PC) species are a common class of phospholipids that comprise the mammalian cell membrane. 1,2-Dioctanoyl PC is a synthetic analog of natural phosphatidylcholine species containing saturated C8:O fatty acids in the sn-1 and sn-2 positions of the glycerol backbone. It exhibits a critical micelle concentration (CMC) value of 0.25 mM at 27°C. 1,2-Dioctanoyl PC serves as an efficient substrate for phospholipase D (PLD) as well as sPLA2 isozymes from bovine pancreas and bee venom.

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.