Fig. 2: Template-assisted covalent modification of DCAF16 and degraders with optimized electrophilic warheads.
From: Template-assisted covalent modification underlies activity of covalent molecular glues
a, TR-FRET signal for DDB1–DCAF16–BODIPY to BRD4BD1-terbium or BRD4BD2-terbium with increasing concentrations of TMX1 (n = 3). b, Intact protein mass spectra of DDB1–DCAF16 alone, DDB1–DCAF16 co-incubated with TMX1 at 4 °C for 16 h or DDB1–DCAF16 co-incubated with TMX1 and BRD4BD2 at 4 °C for 16 h. c, Chemical structures of MMH1, MMH2, MMH1-NR and MMH2-NR. d, Western blot of BRD4 degradation in K562 cells that were treated with DMSO or different concentrations of MMH1, MMH2, dBET6 or MZ1 for 6 h. e, TR-FRET signal for DDB1–DCAF16–BODIPY to BRD4BD2-terbium with increasing concentrations of JQ1, MMH1, MMH2, MMH1-NR and MMH2-NR (n = 3). f, Western blots of BRD4 degradation in K562 cells that were treated with DMSO or different concentrations of MMH1, MMH1-NR, MMH2 or MMH2-NR for 16 h. All western blot data are representative of two independent measurements.
