Functional TRIM24 degraders via conjugation of ineffectual bromodomain and VHL ligands [RNA-seq]

The addressable pocket of a target protein is often not functionally relevant. This is particularly true for multidomain gene regulatory proteins, such as the bromodomain-containing transcriptional regulator TRIM24. TRIM24 has been posited as a dependency in numerous human cancers, yet potent and selective ligands for the TRIM24 bromodomain do not exert effective anti-proliferative responses. We therefore repositioned these probes as targeting features for heterobifunctional protein degraders. RNA-sequencing of MOLM-13 AML cells treated with DMSO, IACS-9571 or dTRIM24 for 4 or 24 hours.