Fig. 6: PROTAC 4 (OICR41114) degrades WDR5 better than PROTAC 1-3.
a PROTAC 4 chemical structure. b Confirmation of DCAF1-PROTAC 4-WDR5 ternary complex formation by SPR. Experiments were performed the same as for PROTAC 1-3 in Fig. 3. Biotinylated DCAF1 was immobilized onto a sensor SA chip. A blank injection was used as a baseline (gray line). PROTAC 4 (black line) and WDR5 (dashed blue line) were injected independently before combining both in a 1:10 ratio of PROTAC with 0.25 µM WDR5 (green line) for ternary complex formation. In the presence of both WDR5 and PROTAC 4, the binding response significantly increased. c PROTAC 4 degraded exogenous WDR5 in cells. The amount of WDR5 was quantified using the exogenous (HiBiT) WDR5 degradation assay as described in Methods. d PROTAC MS67 was used as a control and degraded HiBiT-WDR5 with an EC50 and Dmax values of 3.8 ± 1.0 nM and 78.7 ± 1.8%, respectively. Values are included as average ± SD of biological replicates (n = 4). Source data are provided as a Source Data file.
