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Kinases make intriguing and attractive drug targets. Many are key players in disease-relevant pathways, and it is often relatively straightforward to develop screening assays and identify suitable chemical equity. While a large number of kinase inhibitors have entered the market in the past decade, it can be challenging to design kinase inhibitors with the right safety profile. Both on-target and off-target liabilities may be of concern, especially for non-directly life threatening diseases. This book chapter aims to discuss how to measure, assess, interpret and optimize the selectivity profile of kinase inhibitors, as part of a pro-active safety strategy to design and select drug candidates with an appropriate safety profile.

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