Design principles, molecular structure and properties of JAK PROTACs. (A) PROTAC design strategy. (B) Structures of key intermediates 3 and 4, containing the linker handle. (C) Structures of PROTACs 5 through 8. (D) TREEspot visualization of the kinome selectivity profile of compound (Cmpd) 7 (left panel) and Cmpd 8 at 100 nM concentration (Kinome Scan).