cpla2

Giripladib (PLA695)(PLX-695)是一种cPLA2特异性抑制剂，可抑制辐射诱导的内皮细胞磷酸化ERK 和磷酸化Akt 的增加。

MAFP (Methyl Arachidonyl Fluorophosphonate) 是选择性，针对活性位点，不可逆的 cPLA2 和 iPLA2 抑制剂。 MAFP 也是一种有效的不可逆的 anandamide amidase 抑制剂。

cPLA2α-IN-2 (Compound 122) 是一种针对细胞质磷脂酶 A2α (cPLA2α) 的抑制剂。

FAAH/cPLA2α-IN-1为FAAH及cPLA2α的双重抑制剂，IC50值分别为32 nM和47 nM。

PFK158 是一种选择性的PFKFB3抑制剂，IC50值为 137 nM。它可减少癌细胞中葡萄糖的摄取，ATP 的产生，乳酸的释放，并诱导细胞凋亡和自噬。它还可以增强 Colistin 对细菌的抵抗力，具有广泛的抗肿瘤活性。

Ecopladib (PLA 725) 是一种胞浆磷脂酶 A2α (phospholipase A2α) 抑制剂，在 GLU micelle 和大鼠全血细胞中，IC50 值分别为 0.15 μM 和 0.11 μM。

Fluticasone propionate (CCI-187881) 是一种选择性糖皮质激素受体激动剂，是一种局部抗炎激素，亲和力KD 为 0.5 nM。具有抗病毒活性。

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.

D-Erythro-dihydrosphingosine (C18-Dihydrosphingosine) 可抑制花生四烯酸的释放和cPLA2α活性。

Efipladib is a phospholipase inhibitor. Efipladib decreases nociceptive responses without affecting PGE2 levels in the cerebral spinal fluid.

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.

CAY10650 是高效的胞浆磷脂酶A2α抑制剂，IC50=12 nM，能够抑制脂滴形成和 PGE2 分泌。

AACOCF3（Arachidonyl trifluoromethyl ketone）是一种细胞可渗透的三氟甲基酮类花生四烯酸模拟物。它是一个强效且选择性的85-kDa胞质型磷脂酶A2（cPLA2）缓慢结合抑制剂。通过阻止钙离子载体挑战的血小板中花生四烯酸和12-羟基二十四碳五烯酸的生成，AACOCF3抑制了它们的合成。此外，AACOCF3还能抑制从分离的大鼠岛细胞中诱导的葡萄糖引起的胰岛素释放。鉴于其多样的应用，AACOCF3对心血管疾病研究具有潜在的应用价值。

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。

PF 5212372（PLA-950，ZPL-521，ZPL 5212372）是一种针对cPLA2的高效、选择性抑制剂。

BRI-50460是一种能够穿过血脑屏障的胞质钙依赖性磷脂酶A2 (cPLA2) 抑制剂，具有IC50值为0.88 nM。通过抑制cPLA2，BRI-50460调节炎症脂质信号通路，减轻淀粉样蛋白β42低聚物对cPLA2激活、tau蛋白过度磷酸化以及突触和树突减少的影响，从而发挥调节神经炎症和恢复脂质稳态的活性。此化合物适用于阿尔茨海默病及其他神经退行性疾病研究。

VI-60 是一种口服活性的cPLA2和COX-2双重抑制剂，能够通过抑制p38 MAPK/cPLA2/COX-2/PGE2信号通路，展现出抗炎症的效果。

AVX-001, a cytosolic phospholipase A2 (cPLA2) inhibitor, is used potentially for the treatment of psoriasis.

Tanshinone I (Tanshinone A) 是IIA 型人重组sPLA2(IC50=11 μM)和兔重组cPLA2(IC50=82 μM)抑制剂。

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

10-Pyrene-PC is a substrate for all PLA2s with the exception of cPLA2 and PAF-AH. Upon phospholipid hydrolysis, 10-pyrenyldecanoic acid is produced from 10-pyrene-PC. The monomeric 10-pyrenyldecanoic acid exhibits fluorescence (excitation 345 nm, emission 395 nm), allowing quantitation of phospholipase activity.

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.

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.

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.