Virtual screening approaches for the identification of non-lipid autotaxin inhibitors.

Autotaxin (ATX, NPP-2) catalyzes the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a mitogenic cell survival factor that stimulates cell motility. The high expression of both ATX and receptors for LPA in numerous tumor cell types has produced substantial interest in exploring ATX as an anticancer chemotherapeutic target. ATX inhibitors reported to date are analogs of LPA, a phospholipid, and are more hydrophobic than is typical of orally bioavailable drugs.