Figure 4.
Napthiridinone degrader 6 (dBRD9) offers improved biochemical and cellular selectivity. A) Selectivity of phage-displayed bromodomain displacement by 5 (Bromoscan). B) Chemical structure of dBRD9. C) Immunoblot of BRD9 and actin after 4hr treatment of MOLM-13 cells with indicated concentrations of dBRD9. D) Selectivity of phage-displayed bromodomain displacement by dBRD9 (Bromoscan). E) Compound-induced ternary complex formation of recombinant BRD9(bd) and CRBN-DDB1 (AlphaScreen quadruplicate means +/− SEM). F) Compound-induced ternary complex formation of recombinant BRD4(1) and CRBN-DDB1 as in (E). G) Immunoblot for BRD7 and actin after 4hr treatment of MOLM-13 cells with indicated concentrations of 5 or dBRD9. H) Immunoblot for BRD4 following treatment as in (G).