Comprehending the significance of protein kinases in diseases such as cancer is pivotal for advancing drug development. Scientists at Okayama University uncover a groundbreaking inhibitor aimed at Adaptor Protein 2-Associated Protein Kinase 1 (AAK1). Credit: Hiroshi Tokumitsu, Okayama University
Enhancing drug development for life-threatening diseases like cancer hinges on a deep understanding of protein kinases, making it a focal point for researchers. These enzymes, encoded by more than 500 human genes, serve as critical players in cellular signaling pathways.
However, if these signals are dysregulated, they can disrupt the normal cellular mechanisms, leading to diseases such as cancer. Protein kinase inhibitors have therefore provided a promising avenue in therapeutic intervention to disrupt the aberrant signaling mechanisms underlying such diseases.
Due to the similarity and complexity of kinase structures, the development of effective kinase inhibitors has so far presented a formidable challenge for researchers. Finding specific inhibitors among various potential targets has been a hurdle, until now.
A team led by Professor Hiroshi Tokumitsu from the Graduate School of Interdisciplinary Science and Engineering in Health Systems at Okayama University, along with a graduate student Ms. Akari Yoshida and Dr. Satomi Ohtsuka from Okayama University with Professor Ulf J. Nilsson from Lund University and Professor Teruhiko Ishikawa from the Graduate School of Education at Okayama University, published a study in Scientific Reports on 20 March 2024. The study sheds light on a novel inhibitor targeting Adaptor Protein 2-Associated Protein Kinase 1 (AAK1).
Talking about the inspiration, Prof. Tokumitsu states, “Through years of dedicated research into intracellular signaling mechanisms, we’ve crafted protein kinase inhibitors as potent analytical instruments for fundamental life sciences.” And now it was time to see their achievements in action.”
Their study introduced an innovative method utilizing Kinobeads technology. This cutting-edge approach enabled the team to explore the interactions between TIM-063, originally formulated as a Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, and numerous protein kinases, with a particular focus on AAK1. Through immobilization onto sepharose beads, TIM-063-sepharose complexes were created to capture target kinases from cellular extracts selectively.
2024-05-24 10:00:03
Original from phys.org