Discovery of Potent Small-Molecule Inhibitors of WDR5-MYC Interaction
| العنوان: | Discovery of Potent Small-Molecule Inhibitors of WDR5-MYC Interaction |
|---|---|
| المؤلفون: | Jian Ding, Guo Li, Hejun Liu, Lulu Liu, Ying Lin, Jingyan Gao, Guoqiang Zhou, Lingling Shen, Mengxi Zhao, Yanyan Yu, Weihui Guo, Ulrich Hommel, Johannes Ottl, Jutta Blank, Nicola Aubin, Yi Wei, Hu He, David R. Sage, Peter W. Atadja, En Li, Rishi K. Jain, John A. Tallarico, Stephen M. Canham, Ying-Ling Chiang, He Wang |
| المصدر: | ACS Chemical Biology. 18:34-40 |
| بيانات النشر: | American Chemical Society (ACS), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Molecular Medicine, General Medicine, Biochemistry |
| الوصف: | WD repeat domain 5 (WDR5) is a member of the WD40-repeat protein family that plays a critical role in multiple processes. It is also a prominent target for pharmacological inhibition in diseases such as cancer, aging, and neurodegenerative disorders. Interactions between WDR5 and various partners are essential for sustaining its function. Most drug discovery efforts center on the WIN (WDR5 interaction motif) site of WDR5 that is responsible for the recruitment of WDR5 to chromatin. Here, we describe the discovery of novel WDR5 inhibitors for the other WBM (WDR5 binding motif) pocket on this scaffold protein, to disrupt WDR5 interaction with its binding partner MYC by high-throughput biochemical screening, subsequent molecule optimization, and biological assessment. These new WDR5 inhibitors provide useful probes for future investigations of WDR5 and an avenue for targeting WDR5 as a therapeutic strategy. |
| تدمد: | 1554-8937 1554-8929 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6be8f58a3f8f57cbd62279d195187665 https://doi.org/10.1021/acschembio.2c00843 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....6be8f58a3f8f57cbd62279d195187665 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15548937 15548929 |
|---|