Massively Parallel SPR-Based Fragment Screening of Kinase Arrays

Introduction

Kinases provide a wealth of opportunities for addressing human disease, but their presence in so many critical cellular functions presents challenges for developing drugs with the proper selectivity profiles for maximal therapeutic, and minimal toxic, effect.  Direct label-free approaches, such as SPR, can complement activity assays by providing the intrinsic affinity, while observing the real-time kinetics, of interactions. In this poster, we highlight the power of combining an extensive panel of ready-made biotinylated kinases with HT-SPR to generate a wealth of compound binding information that can augment the drug discovery process with broader selectivity profiling in less time for less cost. Here we highlight the power of combining an extensive panel of ready-made biotinylated kinases with HT-SPR to generate a wealth of compound binding information. In three days over 125,000 interactions were measured between a panel of kinases and the Maybridge 1000 fragment library. We also profiled a kinase-focused small molecule library and obtained more than 80,000 binding interactions in a three-day instrument run. Detailed kinetics were then subsequently obtained for hits of interest. Beyond simple yes/no reporting, this approach allows for nuanced kinetic profiling for up to hundreds of binding events in parallel, thereby enabling thoughtful discovery of safe and efficacious drug candidates.

Posted by Anthony Giannetti