Definition

An orally bioavailable ligand directed degrader (LDD) 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, with potential antineoplastic activity. Upon oral administration, BCL6 degrader BMS-986458 specifically and simultaneously targets and binds to BCL6 on tumor cells and 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, overexpressed in certain tumor cells, serves an important role in cell signaling and tumor cell proliferation.