Development of dual inhibitors of BET bromodomains and JAK2. (A) Chemical structures of TG101348 and TG101209. (B) X ray cocrystal structure of TG101348 bound to BRD4(1) (PDB ID: 4OGJ). (C) SARs of dual inhibitors of BET bromodomains and JAK2. Protein is represented by gray ribbons, with key compound-contacting residues indicated by yellow sticks. The compound is shown in sticks and colored according to the atom type (C, light blue; N, blue; O, red; S, yellow). Black dashed line = hydrogen bond; orange sphere = water molecule