phospholipase a2, group iia

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.

GK241 (compound 31a-c), a 2-oxoamide-based compound, exhibits inhibitory activity against group IIA secretory phospholipase A2 (GIIA sPLA2) in humans and mice, with IC50 values of 143 nM and 68 nM, respectively. The mechanism of inhibition has been explored through molecular dynamics simulations.

CGP 43182 is an effective inhibitor of group IIA secretory phospholipase A2 (Group IIA sPLA2) activity in vitro, which can be used to prevent the synergistic effect of pro-inflammatory genes stimulated by cytokines mediated by NFkappaB.

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.

Varespladib sodium (LY315920 sodium) is a highly potent and selective inhibitor of group IIA secretory phospholipase A2 (sPLA2), with an IC50 of 9 nM. It shows significant inhibitory activity against sPLA2 in serum samples from multiple species, including rat (IC50 of 8.1 nM), rabbit (IC50 of 5.0 nM), guinea pig (IC50 of 3.2 nM), and human (IC50 of 6.2 nM).