The potential role of Autotaxin (ATX) in physiological and pathological processes turned it
in an attractive drug target for pharmacological therapeutic development. However, potent and selective
non-lipid as well lipid inhibitors of ATX are currently not available as drugs. In this paper we tried
to review all the known progress on ATX inhibition using two dimensional (2D)-Quantitative Structure
Activity Relationship (QSAR) and three dimensional (3D) mapping techniques. Furthermore, we
tried to compare and extract conclusions analyzing with 3D mapping techniques vastly diverse structures
of non-lipid ATX inhibitors which have been reported in patents. McGowan’s Volume (MgVol)
molar volume and Molar Refractivity (MR) of substituents seems to govern the ATX inhibition. 3D-mapping results point
to the role of steric properties (Volume and Polar Surface Area-PSA). Steric factors are obviously important. The role of
hydrophilicity was also highlighted. Electronic parameters are not found to be present.
Keywords: 2D-QSAR, 3D-mapping, autotoxin inhibitors, inflammation, lipid mediators, non lipid, PK descriptors.
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