DBr-1

DBr-1 is a DCAF1-BRD9 PROTAC, created by linking the BRD9 binder BI-956448 to the DCAF1 scaffold via a piperidine-aliphatic carbon linker. It is a potent and selective degrader of BRD9 with a DC50 of 90 nM. It overcomes intrinsic resistance to VHL-degraders, positioning DCAF1-PROTACs as a promising strategy to counter ligase-mediated resistance.