Figure 1
From: Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera
CRBN is efficiently degraded by VHL-CRBN heterodimerizing PROTACs. (A) Schematic diagram of the PROTAC containing pomalidomide and the VHL ligand (VH032). (B) Structure of TD-158, TD-165, TD-343, and TD-487. (C) HEK293T cells were treated with TD-158, TD-165, TD-343 or TD-487 (0.1, 1, and 10 μM) for 24 h, and VHL protein levels were analyzed by immunoblotting. L.E. indicates long exposure of the Western blot. (D) DC50 graph of TD-158 and TD-165 compounds (TD- 165, DC50 = 20.4 nM; TD-158, DC50 = 44.5 nM). (E) HA-CRBN and Flag-VHL were expressed in HEK293T cells. After 24 h, the cells were treated with TD-158 (500 nM) for 24 h. Whole cell lysates were analyzed by immunoblotting for the indicated proteins. (F) HEK293T cells were treated with 500 nM TD-158 at different time points, and CRBN levels were analyzed by immunoblotting. L.E. indicates long exposure of the Western blot.
