Protein kinases function as key ‘control switches’ in cells, regulating growth, communication and responses to stress. While they have long been a central focus of drug development, most existing therapies are designed to inhibit kinase activity, particularly in cancer. However, in many common conditions, including cardiovascular, metabolic and neurodegenerative diseases, kinase activity is reduced rather than excessive. Safely restoring this activity has remained a significant scientific challenge.
In a study published in Cell (He et al Rational discovery of therapeutic PAK1 allosteric activators), an international team led by Professor Ming Lei from the Department of Pharmacology at the University of Oxford – working with collaborators across the UK, Germany, Poland, the United States and China – reports a new strategy (as illustrated in the figure above) to address this problem.
A major challenge in drug development lies in hit discovery, the initial stage of identifying small molecules that interact with a biological target to produce a desired effect. Conventional methods, particularly high-throughput screening (HTS), involve testing millions of compounds but are often inefficient in identifying suitable candidates.
Read the full story on the Department of Pharmacology website.