Discovery of potential integrin VLA-4 antagonists using pharmacophore modeling, virtual screening and molecular docking studies.

Very late antigen-4 (VLA-4) is an integrin protein, and its antagonists are useful as anti-inflammatory drugs. The aim of this study is to discover novel virtual lead compounds to use them in designing potent VLA-4 antagonists. A best pharmacophore model was generated with correlation coefficient of 0.935, large cost difference of 114.078, comprising two hydrogen bond acceptors and three hydrophobic features. It was further validated and used in database screening for potential VLA-4 antagonists. A homology model of VLA-4 was built and employed in molecular docking of screened hit compounds. Finally, two compounds were identified as potential virtual leads to be deployed in the designing of novel potent VLA-4 antagonists.