Kinases are one of the most widely-studied drug target classes, with over 20 years in the spotlight for drug discovery research. Selecting optimized assays for screening, hit validation, selectivity profiling, and lead optimization, represents key steps towards identifying candidate compounds for preclinical and clinical development. With over 500 related proteins in the kinome, the path to candidate selection is not always straightforward and can often require more complex assay development to properly interrogate kinase activity in both enzymatic and cellular contexts.
This webinar will discuss the need for both targeted activity, as well as appropriate selectivity, as key requisites in the discovery of new kinase therapeutics. Since many kinase inhibitors often behave similarly, the need to demonstrate selectivity is paramount, especially with therapeutic indications where a broader profile is undesirable. Transitioning into a cellular context is essential in kinase drug discovery, where an inhibitor must be able to function in a much more complicated environment. Within the cellular context, the inhibitor must be able to demonstrate not only mechanistic activity at the target, but also a functional effect on the cell. Ultimately, this should result in a kinase inhibitor for therapeutic application that demonstrates specific activity at the intended target, while also being selective enough that its therapeutic goal is achieved, without causing unmanageable toxicity.
- Understand historical trends and challenges in developing kinase inhibitors
- Identify key principles in developing assays for screening and hit validation
- Balance the importance of target coverage and selectivity
- Improve your decision making by also leveraging cellular mechanistic assays
- Develop functional assays to help guide and select in vivo efficacy models
Dr. Alastair King
Group Leader, Cell-based Profiling
Eurofins Pharma Discovery Services
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