Taken together, the data shows that while 1 and 2 can induce degradation of BET proteins by engaging either ligase, the induced degradation activity was not comparably driven by each E3 ligase, and that there remained a strong non-degrading component to the compound's cellular antiproliferative activity. We therefore sought to develop a larger and more diverse set of heterotrivalent PROTACs to expand the chemical space, and to improve on the characteristics presented by 1 and 2.