Strategies to generate biological reagents for kinase drug discovery

High-throughput screening (HTS) has been and is likely to remain one of the most widely used tools for Hit identification in the pharmaceutical, biotechnology and academic sectors. It has evolved into a highly integrated and automated process enabling the screening of millions of compounds in a timely manner. It is of paramount importance that appropriate biological reagents are utilized in an HTS campaign as their quality and physiological relevance will influence the likelihood of the activities of any identified Hits translating in vivo.

This article covers the strategies that can be used to efficiently design and generate biological reagents for the development of kinase assays and their subsequent use in HTS campaigns. The authors describe the variety of molecular biology and expression methodologies available to yield biological reagents of high quality, physiological relevance and amenable to kinase drug discovery.

The techniques now available for gene cloning and protein expression are vast and can be overwhelming. Therefore, we provide guidelines for the most effective route to generate high quality, physiologically relevant biological reagents for kinase drug discovery. The methods available for the generation of biological reagents have undergone significant advances and some of these have been driven by the requirements of HTS campaigns. If the approaches described herein are implemented, it is anticipated they will result in the generation of suitable biological reagents for the development of kinase assays for HTS campaigns.