Extended Data Fig. 1: IBG1 degrades BRD2 and BRD4 independent of DCAF15.

a,b, Structure (a) and BET protein degradation (b) of sulfonamide-based PROTAC DAT389. HeLa cells were treated with increasing concentrations of MZ1 or DAT389 for 16 h and BET protein levels were analysed by immunoblot (n = 1). c, Cytotoxicity of IBG1 and VHL-based PROTAC MZ1. MV4;11 and HCT-116 cells were treated with increasing concentrations of compounds for 24 or 96 h, respectively, and cell viability was assessed via CellTiterGlo assay. Dose-response curves were fitted using non-linear regression. n = 2 biological replicates, mean +/− s.d. d, End-point HiBiT protein degradation. BRD2, BRD3 or BRD4 HiBiT knock-in HEK293 cells were treated with the indicated compounds for 5 h and levels of HiBiT-tagged proteins were quantified via the HiBiT lytic detection system. Dose-response curves were fitted using non-linear regression. n = 3 independent experiments, mean +/− s.d. e, Degradation activities of IBG1. BET protein levels were quantified by immunoblotting after compound treatment in HEK293, HCT-116 WT and DCAF15 KO cells. n = 3 independent experiments, mean +/− s.d. Source data, Supplementary Fig. 1. f,g, In-cell mechanistic evaluation of IBG1. HCT-116 WT (f) or DCAF15 knockdown (g) cells were treated for 2 h with E7820 (1 µM) or IBG1 (10 nM) alone, or after 1 h pre-treatment with JQ1 (10 µM), MG132 (50 µM) or MLN4924 (3 µM). Western blot representative of 3 (f) or 2 (g) independent experiments.