Considering autotaxin inhibitors in terms of 2D-QSAR and 3D-mapping- review and evaluation.
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.
Sotirios
S
Katsamakas
Eleftherios
E
Bermperoglou
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. hadjipav@pharm.auth.gr.
Dimitra
D
Hadjipavlou-Litina
D019540:Area Under Curve; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006207:Half-Life; D056004:Molecular Dynamics Simulation; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D000099189:Lysophospholipase D
D004791:Enzyme Inhibitors; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D