Fig 1: Designed Raman-active CRBN based PROTACs are potent BET degraders. (a) Chemical structures of BET bromodomain inhibitor (+)-JQ1, CRBN ligands lenalidomide and 1, and Raman-active probe BADY. (b) Designed Raman-active PROTACs LS1–LS4 bearing CRBN E3 ligase ligands. (c) Representative western blot after 24 h treatment of HeLa cells with DMSO, MZ1, cisMZ1, LS1, LS2, LS3 and LS4. (d) BRD4 quantification by western blot following the treatment conditions described in (c). Bars represent the mean ± SD from n = 3 biological replicates. Statistical analysis was performed using one-way ANOVA compared to DMSO; **** p < 0.0001. (e) Quantitative whole proteome analysis of HeLa cells after 6 h treatment with 30 nM of LS1 or LS2, compared to DMSO treatment (n = 4 biological replicates).