To determine if SIM1 could induce a conformational change of BRD4, known to occur with bivalent BET inhibitors , we utilized a NanoBRET biosensor containing the BD1-BD2 tandem domains of WT BRD4 or mutant N433F, flanked respectively by a NanoLuc donor and HaloTag acceptor (Fig. ). With the BD1-BD2 tandem WT biosensor, compounds SIM1, cis-SIM1 and MT1 all showed a change in BRD4 conformation, manifested by an increase in NanoBRET signal which reached and maintained a plateau, as expected for an intramolecular engagement (Fig. ). As control, the BD1-BD2 N433F mutant sensor showed no response indicating that simultaneous binding of BD1 and BD2 is required for the conformation change (Fig ).