With compounds 93 -95 in hand, we validated their on-target BRD4 degradation activity in parental (WT VHL and CRBN expression), CRBN KO, and VHL KO cell lines all expressing endogenous HiBiT-BRD4 (Supplementary Figure ). As expected, 95 showed no degradation of BRD4 in any of the cell lines, owing to its inability to engage either ligase, while 93 was inactive in VHL KO cells, and 94 was inactive in CRBN KO cells. While the potency of 93 was decreased relative to 27 in parental and CRBN KO cells, 94