(A) Structures of small molecule inhibitors targeting USP7. (B) The binding characteristics of current inhibitors of USP7. The catalytic triad of the catalytic domain is shown as red spheres. Compounds P50429 and P22077 both bind to this region. The allosteric inhibitors (GNE6640 and GNE6776, shown in orange) occupy a functional site that is 12 Å away from the catalytic cysteine. The pyrimidinone analogs (shown in blue) bind to the catalytic region that is normally occupied by the C terminus of ubiquitin (shown in cyan).