The transmembrane enzyme KIAA1363 (also known as AADACL1) controls the production of the monoalkylglycerol ether (MAGE) class of neutral ether lipids (NELs) in cancer cells. Hyperactivity of this 2-acetyl MAGE hydrolase is associated with tumor cell migration, invasion, survival, and growth. JW 480 acts as a potent, selective inhibitor of KIAA1361 (IC50s = 20 nM in mouse brain membrane proteomes and 6-12 nM in human PC3 prostate cancer cell proteomes), showing little cross reactivity with hormone-sensitive lipase, acetylcholinesterase, or other serine hydrolases. JW 480 is active in vivo, reducing PC3 tumor xenograft growth in immune-deficient SCID mice at an oral dose of 80 mg/kg.
