The initial incentive behind the creation of IniXium was the firm belief that fragment screening was going to become the ultimate tool for rapid and efficient drug discovery. History shows that this method has delivered on its promises. IniXium is contributing to increase the success rate of fragment-based screening (FBS) by establishing new paradigms for fragment screening. We designed a fragment library optimized for crystal complex formation. For us, optimized means high solubility and absence of soluble aggregates at the highest possible concentration; two parameters that often hinder complex formation during crystallization. We offer two strategies for FBS. One is affinity-selection mass spectrometry (AS-MS) that is based on the enrichment of binders by ultrafiltration prior to detection by mass spectrometry. This rapid method provides hits that can be moved to crystallography in less than a month with very little protein consumption. In the second strategy, a subset of the most soluble fragments (300) are used directly for crystal soaking. This allows for a faster hit identification, and structures are instantly available to initiate your medicinal chemistry campaign. Our fragment screening campaigns are followed by a round of “analogue by catalogue”. Virtual screening tools are also used for analogue selection. Structures of these analogues will provide validation of the hits and their binding mode. We then stay on to provide crystallography support for ligand optimization.
