()-AS 115

KIAA1363 is a 2-acetyl monoacylglyceryl ether (MAGE) hydrolase that is upregulated in aggressive cancers from various tissues.¹ The enzyme catalyzes the hydrolysis of the 2-acetyl MAGE to MAGE and serves as a central enzyme in the PAF and LPA signaling network.² AS 115 is a potent and selective inactivator of KIAA1363, displaying an IC₅₀ value of 150 nM when tested as a racemic mixture in the invasive ovarian cancer cell line SKOV3.² Treatment of SKOV3 cells with 10 μM AS-115 for 4 hours significantly reduced the formation of MAGE, alkyl-lysophosphatidylcholine, and alkyl-lysophosphatidic acid. The activity of the individual enantiomers of AS 115, i.e. (+)-AS 115 and (?)-AS 115, has not been determined.

1. Jessani, N., Liu, Y., Humphrey, M., et al. Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness Proc. Natl. Acad. Sci. USA 99(16),10335-10340(2002).
2. Chiang, K.P., Niessen, S., Saghatelian, A., et al. An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling Chem. Biol. 13(10),1041-1050(2006).