cpla2α

FAAH cPLA2α-IN-1 is a dual inhibitor of FAAH and cPLA2α, with potent inhibitory activity, exhibiting half-maximal inhibitory concentrations (IC50s) of 32 nM for FAAH and 47 nM for cPLA2α [1].

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.

D-Erythro-dihydrosphingosine (C18-Dihydrosphingosine) inhibits arachidonic acid release and cPLA2α activity.

GK420 (AVX420) is a potent inhibitor of cytoplasmic phospholipase A2α (cPLA2α), with an XI(50) value of 0.0016. It effectively inhibits the release of arachidonic acid, with an EC50 of 0.09 μM. GK420 plays a significant role in cancer research.

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

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.

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.

Cytosolic phospholipase A2α (cPLA2α) specifically catalyzes the hydrolysis of arachidonic acid from thesn-2-ester position of membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes, both important mediators of the inflammatory process.1CAY10641 is an inactive alcohol derivative of a highly potent (IC50= 12 nM) cPLA2α inhibitor.2The parent compound demonstrates strong anti-inflammatory effects when applied topically at a dose of 0.1 mg/ear in a mouse model of acute irritant contact dermatitis.2CAY10641 is rapidly cleared from the blood stream (only 0.5 μg/ml remains 30 minutes after 10 mg/kg intravenous administration to mice).2However, no other biological effects have been reported. 1.Schaloske, R.H., and Dennis, E.A.The phospholipase A2 superfamily and its group numbering systemBiochemica et Biophysica Acta17611246-1259(2006) 2.Drews, A., Bovens, S., Roebrock, K., et al.1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A2α with reduced lipophilicity: Synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activityJournal of Medicinal Chemistry535165-5178(2010)

Potent and selective cytosolic phospholipase A2 alpha (cPLA2α) inhibitor (IC50 = 20 nM). Selective for cPLA2α over secreted PLA2α (sPLA2α; exhibits no inhibition at 10 μM). Inhibits cPLA2α-dependent inflammatory responses in vitro in guinea pig and human whole-blood assays. Improves diet-induced liver injury and CCl4-induced hepatic fibrosis in vivo. Orally bioavailable.

ASB14780 is a 4-phenoxy derivative and an inhibitor of cytoplasmic phospholipase cPLA2α (IC50: 20 nM).

CAY10650 is an effective inhibitor of cytosolic phospholipase A2α (cPLA2α, IC50: 12 nM).