4.8 nM and 1.6 nM, for BRD3; and, 14 nM and 15 nM, for BRD2, respectively (Table ). 26 and 27, which have 5-C tethering, were an average of 3.4-fold more potent than their 4-C tethered counterparts AB3062 and AB3066 , respectively. Interestingly, the additional methyl group on the benzylic position of the VHL ligand present in 27 and 24 had no significant effect on BET degradation when comparing to their nonmethylated matched pairs 26 and 23 respectively. However, the modification did lead to an unfavourable ~2.6fold increase in CRBN degradation.