Boronic Acid Based Inhibitors of Autotaxin: Understanding their Biological Role in Terms of Quantitative Structure Activity Relationships (QSAR)

Sotirios      Katsamakas; Dimitra      Hadjipavlou-Litina

Abstract

Autotaxin (ATX or NPP2) is a newly discovered secreted glycoprotein lyso-phospholipase D (lysoPLD). Its main role is the lysoPLD activity, which transforms lyso-phosphatidylcholine (LPC) into lyso-phosphatidic acid (LPA). ATX contributes to tumor progression, inflammation, obesity and diabetes and constitutes a target for drug design. Various synthetic phospholipid analogues have been explored as ATX inhibitors. However, potent and selective non-lipid inhibitors of ATX are currently not available. Some new ATX inhibitors have been subjected to a Quantitative-Structure Activity Relationships (QSAR) analysis. CMR represents the calculated molar refractivity of the molecules and seems to govern the ATX inhibition. Steric factors are obviously important. No role for lipophilicity was found. Electronic parameters are not found to be present.

Keywords: Boronic Acid based Autotaxin Inhibitors, Hydrophobicity, Molar Refractivity, QSAR, lyso-phosphatidic, cell proliferation, phospholipase, macromolecular systems