We next moved to study compounds in a BET-sensitive cell line, the prostate cancer line 22Rv1. Treatment of 22Rv1 cells with varying concentrations of compounds at 4h confirmed the enhancement in BET degradation potency and cMyc level suppression activity of SIM1 compared to MZ1 and ARV-771, as well as non-degrading controls MT1 and cis-SIM1 (Fig. and Extended Data Fig. ). The expected mechanistic dependency of SIM1-induced degradation on functional E3 ligase and proteasomal activity was confirmed with co-treatment with VHL inhibitor VH298 (11) and proteasome inhibitor MG132 (Extended Data Fig. ).