X-Ray co-crystallography of WDR5 bound to WBM-site inhibitors. A) An overlay of the X-Ray co-crystal structure of 5g (green, PDB: 6U80) and 1 (grey). There are few major changes in the protein orientation, but 5g diminished binding affinity compared to 1, suggesting the upward frame-shift affords an unfavorable position of the small molecule ligand; B) Structure of 6b bound to WDR5 (PDB: 6U8B), key residues are shown as sticks, highlighting hydrogen and halogen bonding interactions between the ligand and protein; C) Structure of 5n bound to WDR5, demonstrating the orientation of the nitrile toward the protein (PDB: 6U8O); D) Structure of 6g bound to WDR5 (PDB: 6U8L). E) Structure of 7k bound to WDR5 (PDB: 6U5Y); F) Structure of 7u bound to WDR5 (PDB: 6U5M).