BCL6 degrader ARV-393

An orally bioavailable, targeted degrader composed of an E3 ubiquitin ligase-binding moiety that is conjugated, via a linker, to a B-cell lymphoma 6 protein (BCL6; BCL-6)-binding moiety using the proteolysis targeting chimera (PROTAC) technology, with potential antineoplastic activity. Upon oral administration of BCL6 degrader ARV-393, the BCL6-binding moiety specifically targets and binds to BCL6 on tumor cells while the E3 ubiquitin ligase-binding moiety targets and binds to E3 ubiquitin ligase, thereby creating a ternary complex. This induces E3 ligase ubiquitination and proteasome-mediated degradation of BCL6. This prevents BCL6-mediated signaling and activation of downstream survival pathways. This leads to an inhibition of the growth of tumor cells that overexpress BCL6. BCL6, a transcriptional repressor overexpressed in certain tumor cells, serves an important role in cell signaling and tumor cell proliferation.