LFA-1/ICAM-1interaction inhibitors

Computer aided drug designing 

studies on pharmacological

inhibitors LFA-1 

Lymphocyte function-associated antigen - LFA

Inter-Cellular Adhesion Molecule - ICAM

The LFA-1/ICAM interaction can be disrupted at the site of LFA-1/ICAM interaction, the metal-ion-dependent adhesion site (MIDAS), or through binding to an allosteric site (I domain allosteric site, IDAS) on LFA-1 that causes it to adopt a conformation that cannot bind to ICAM. Binding to the MIDAS site has been successfully achieved through peptide and peptidomimetic strategies by researchers at Genentech. Our strategy focused on the allosteric site through modification of a series of molecules. Herein, we describe the in silico study of a series of potent inhibitors of the LFA-1/ICAM interaction by utilizing an Analogue-based drug design approach and Structure-based drug design

This study indicates that there are several factors that influence the biological activity of LFA-1 inhibitors