TRIM24 (PHD-Bromo) X-ray complexes of initial virtual screening hit and lead templates. (A) Compound 1 bound to TRIM24 (1.9 Å resolution) bromodomain (grey ribbon), PHD domain (black), N980 (cyan), and Zinc (magenta) are depicted (PDB 4YAB). (B) Acetyllysine binding site with 1, lipophilic residues L922, A923, and F924 on the ZA-loop and V986 on the BC α-helix form an “LAF/V-shelf” (yellow sticks) (PDB 4YAB). (C) Complex of 3b (1.7 Å resolution) shown in two poses based upon partial occupancy, second pose (purple) in ZA-channel (PDB 4YAD). (D) Complex of 5b (2.2 Å resolution) with arylsulfonamide interacting with LAF/V-shelf (PDB 4YAT).