S-2474 is an inhibitor of COX-2 and 5-lipoxygenase, with IC50s of 11 nM and 27 μM for COX-2 and COX-1 in human intact cells, and used as a nonsteroidal anti-inflammatory drug. S-2474 is an inhibitor of COX-2 and 5-lipoxygenase, with IC50s of 11 nM and 27 μM for COX-2 and COX-1. S-2474 prevents neurons from Aβ-induced cell death significantly in a concentration-dependent manner (IC50 =26±12 nM). S-2474 (10 μM) completely inhibits Aβ(25-35)-induced neuronal cell death. S-2474 also shows neuroprotective effects in the Aβ(1-40)-induced neuronal cell death. S-2474 inhibits the PGD2 generation in a concentration dependent manner (IC50=69.8±21.9 nM). S-2474 (10 μM) lowers the elevated level of PGD2 significantly and reduces radicals from Aβ(25-35)-treated neurons. S-2474 significantly prevents neurons from undergoing sPLA2-IIA-induced cell death. S-2474 completely ameliorates sPLA2-IIA-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Moreover, S-2474 significantly inhibits the sPLA2-IIA-induced generation of PGD2. S-2474 inhibits sPLA2-IIA-induced neuronal cell death in a concentration-dependent manner (IC50 = 94 nM).