Secreted phospholipases A2 (sPLA2s) are a diverse family of low molecular weight PLA2s with tissue-specific expression patterns and actions. The group IIA sPLA2 (sPLA2-IIA) was originally purified from platelets and exudates from patients with rheumatoid arthritis. Its expression can be induced by inflammatory mediators, and mouse studies suggest that it may play roles in colorectal polyposis, atherosclerosis, and bacterial infections. YM-26734 is a derivative of a compound isolated from the fruit of H. amygdaline that competitively inhibits rabbit platelet sPLA2 with an IC50 value of 85 nM. It inhibits sPLA2-hGIIA, -mGIIA, -rGIIA, -hGV, -mGV, -hGX, and -mGX with IC50 values of 80, 30, 120, 110, 520, >1600, and >1600 nM, respectively. YM-26734 displays minimal activity at cytosolic PLA2, COX and lipoxygenase. At 45 μg/ear or 11 mg/kg i.v., YM-26734 has been used to ameliorate local inflammatory responses in TPA-induced mouse ear edema.
