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).

SPLA2:9 nM (IC50)

Treatment with Varespladib sodium (10 μM; 24 and 48 hours; HCjE cells) completely inhibits the retinoic acid (RA)-induced increase in MUC16 protein expression in HCjE cell lysates at both 24 and 48 hours, as confirmed by Western Blot Analysis and RT-PCR. This indicates a 100% inhibition at 24 hours and a 99% inhibition at 48 hours, demonstrating Varespladib sodium's efficacy in significantly reducing RA-induced MUC16 expression in this cell line at the specified concentrations and time points[2].

Varespladib sodium effectively suppresses the release of thromboxane A2 (TXA2) triggered by human sPLA2 from bronchoalveolar lavage cells in isolated guinea pig lungs, with an inhibitory concentration (IC50) of 0.79 μM. Moreover, it has been determined that the effective dose (ED50) of Varespladib sodium is 16.1 mg/kg in male Hartley guinea pigs weighing 300-500 g. When administered intravenously at dosages of 3 mg/kg, 10 mg/kg, and 30 mg/kg, a consistent inhibition of sPLA2 activity in the bronchoalveolar lavage fluid was recorded, alongside a reduction in the sPLA2-induced TXA2 generation in the bronchoalveolar lavage cells of these guinea pigs.