Publication Date
5-7-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2322934121
PMID
38701119
PMCID
PMC11087803
PubMedCentral® Posted Date
5-3-2024
Published Open-Access
yes
Keywords
Humans, Female, Protein Kinase Inhibitors, Endometriosis, DNA, Receptors, Eph Family, Receptor, EphA2, Small Molecule Libraries, Cell Movement, DNA-encoded chemistry, ephrin receptor kinase inhibitors, endometriosis
Abstract
EPH receptors (EPHs) are highly sought-after drug targets owing to their essential roles in maintaining appropriate cellular functions in both physiological and disease conditions. However, limited potency and specificity pose significant obstacles to the development of small-molecule inhibitors for EPHs. Here, using high-throughput DNA-encoded chemical library screenings, we developed potent and selective inhibitors of the EPH receptor kinase family. Our results also emphasize the therapeutic potential of our EPH inhibitors in cancer and endometriosis, a global health concern that causes chronic pain and often leads to infertility in women. This study showcases the robust pipeline of using DNA-encoded chemistry technology to identify nonhormonal therapeutic agents tailored for the treatment of gynecologic diseases, including, but not limited to, endometriosis.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Medical Cell Biology Commons, Medical Genetics Commons, Obstetrics and Gynecology Commons, Women's Health Commons
Comments
See commentary "Deciphering the code: Advancing therapies for endometriosis and cancer with DNA-encoded drug discovery", e2407555121.
Associated Data