ARN 14494 is a potent serine palmitoyltransferase inhibitor (SPT, IC50 = 27.3 nM). ARN 14494 inhibits synthesis of long chain ceramides and dihydroceramides in an in vitro model of Alzheimers diease. The compound prevents the synthesis of proinflammatory cytokines and the oxidative stress-related enzymes iNOS and COX-2 in mouse primary cortical astrocytes. ARN 14494 is neuroprotective against beta-amyloid 1-42 induced neurotoxicity in primary cortical neurons co-cultured with astrocytes.
