Researchers from Centre for Medicines Discovery (CMD), in collaboration with scientists from the Karolinska Institute, Max Planck Institute of Molecular Physiology, Leiden University Medical Center, and Icahn School of Medicine at Mount Sinai have discovered that an enzyme called choline kinase alpha (CHKA) is important for how cells grow and communicate in the body. This enzyme plays a significant role in both cancer and the immune system.
The study found that two chemical compounds (UNC0638 and UNC0737) can target and inhibit CHKA. By doing so, these compounds can slow down or stop the growth of cancer cells. This means that in the future, doctors might be able to use these compounds to treat certain types of cancer more effectively.
The research also showed that when CHKA is inhibited, it affects the immune system, specifically by reducing the production of certain antibodies (IgG) and affecting the development of immune cells (B-cells). This discovery is crucial because it highlights a new way to potentially control immune responses, which could be useful for treating autoimmune diseases.
Figure. Co-crystal structure of one of the investigative compounds bound to human CHKA (PDB: 8BI6).
Scientists from Kilian Huber's lab at CMD elucidated the molecular mechanism by which these compounds bind to CHKA, providing valuable information for developing new drugs.
Ludwig Bauer, who co-led the study, stated: 'This discovery opens up new avenues for therapeutic intervention in cancer and immune-related diseases. The ability to target CHKA with specific inhibitors could transform our approach to treatment.'
Read the full paper on the Angewandte Chemie website: https://doi.org/10.1002/anie.202420149