Carterra LSA^XT characterization of kinase inhibitor selectivity and kinetics

Key Highlights

• Easily measure direct compound binding down to at least 500 Da

• High-capacity array allows for analysis of a broad panel of targets and off-targets

• Both weak- and high-affinity interactions are readily quantitated

Introduction

While phosphorylation plays a critical role in the regulation of many biological processes, when unchecked it can result in cell hypertrophy and contribute to the development of cancer. Hyperactivity of protein kinases is a key driver for unrestricted phosphorylation. Protein kinases as a drug target class present challenges owing to the widespread involvement of phosphorylation across pathways and the sharing of conserved regions among many kinases. As a result, effective targeting of protein kinases must include a strategy to minimize off-target effects.

Following on this, we describe here an approach to screening kinase inhibitors by HT-SPR on the LSA^XT platform. Using the LSA^XT, both quantitative kinetics and selectivity can be determined for up to hundreds of targets and off-targets in parallel. The array format of HT-SPR makes it very practical to screen these hundreds of interactions simultaneously and minimize time and reagent consumption. In addition, the increased sensitivity of the LSA^XT enables confident measure for this class of molecules. While protein kinases are used here as an example, any therapeutic strategy focused on understanding and minimizing off-target effects can benefit from this approach.

Posted by Rebecca Rich