At last week’s American Chemical Society Spring meeting, Bristol Myers Squibb Co. discussed the development of a potent, orally bioavailable and highly selective cereblon (CRBN)-mediated ligand-directed degrader (LDD) of B-cell lymphoma 6 protein (BCL6), BMS-986458, for the treatment of B-cell non-Hodgkin lymphoma.
B-cell lymphoma 6 (BCL6) is an essential transcriptional factor for the humoral immune response. However, genomic deregulation of BCL6 contributes to the development of different types of lymphoma such as diffuse large B-cell lymphoma (DLBCL).
The BCL6 degrader BI-3802 works by inducing polymerization of its target protein, which in turn triggers the addition of ubiquitin tags on the polymerized structure and degradation by the proteasome, scientists reported in the Nov. 18, 2020, issue of Nature.
