Figure 1. Discovery of Small Molecule WIN Site Inhibitors.
(A) Elaboration of fragment hit C1 into our first-generation chemical probe C3.
(B–D) X-ray co-crystal structures of WDR5 bound to (B) the fragment hit C1 (PDB: 6DY7), (C) C2 (PDB: 6E1Y), and (D) C3 (PDB: 6E22).
(E) Elaboration of fragment hit C4 into our second-generation chemical probe C6.
(F–H) X-ray co-crystal structures of WDR5 bound to (F) the fragment hit C4 (PDB: 6E1Z), (G) C5 (PDB: 6DYA), and (H) C6 (PDB: 6E23).
See also Figure S1 and Tables S1 and S2.
