X-ray fragment screening of MEK1 to identify allosteric fragment binders

Abstract

The drug development process includes several phases and often span over many years. The initial phases are directed towards identifying and validating a potential target. Once a target has been validated, the hit identification and lead discovery process is initiated. This project have been performed on behalf of AstraZeneca and aimed to use x-ray crystallography to screen a compound library to identify fragments that binds to the allosteric pocket of MEK1. The results from this screen have mapped how a library of selected small molecules bound to the allosteric site. In total the campaign yielded 24 bound fragments with a good diversity that probes the entire pocket in a eÿcient way.