Gregory Caleb Howard, Jing Wang, Kristie L Rose, Camden Jones, Purvi Patel, Tina Tsui, Andrea C Florian, Logan Vlach, Shelly L Lorey, Brian C Grieb, Brianna N Smith, Macey J Slota, Elizabeth M Reynolds, Soumita Goswami, Michael R Savona, Frank M Mason, Taekyu Lee, Stephen Fesik, Qi Liu, William P Tansey
The chromatin-associated protein WD Repeat Domain 5 (WDR5) is a promising target for cancer drug discovery, with most efforts blocking an arginine-binding cavity on the protein called the 'WIN' site that tethers WDR5 to chromatin. WIN site inhibitors (WINi) are active against multiple cancer cell types in vitro, the most notable of which are those derived from MLL-rearranged (MLLr) leukemias. Peptidomimetic WINi were originally proposed to inhibit MLLr cells via dysregulation of genes connected to hematopoietic stem cell expansion...
April 29, 2024: ELife