Protein kinases (PKs) are involved in a wide variety of signalling pathways and are central to most physiological processes. These enzymes are most often deregulated, hyperactivated or overexpressed, as a result of genetic alterations in human pathologies, including cardiovascular diseases, neurodegenerative and endocrinological disorders, viral infection, cancer and diabetes. As such they constitute attractive targets for development of therapeutics and several small molecule inhibitors have been developed to interfere with their function. Whilst the vast majority of PKIs that have entered clinical trials and have been approved by the FDA target, target the ATP-binding pocket of tyrosine kinases, new strategies are being developed to target conformational transitions and essential protein/protein interactions, thereby yielding new generations of compounds with greater specificity and different mechanisms of action.

This Research Topic will provide an overview of different types of PK inhibitors (PKIs) for different subclasses of PKs and explore the different strategies pursued from conventional targeting of the ATP-binding pocket and/or catalytic site to allosteric modulators.

We welcome original research and review articles from researchers involved in the whole sphere of PKI chemical biology. Topics included in this collection are;

• Chemical biological probes of KI efficacy and efficiency in vitro and in vivo
• Allosteric modulators of kinases
• ATP-competitive inhibitors
• KI that target cellular processes such as kinase degradation
• Understanding off-targets of KI and the mechanisms of disease resistance
• Biophysical/biochemical probes of PKI structure/interactions and dynamics
• Computer assisted design of KI, computational modelling of KI structure, KI dynamics and interactions with protein surfaces, machine learning and artificial intelligence (AI) approaches to KI design

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Frontiers in Chemistry

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