BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high-affinity antibodies of different isotypes[1]. Bcl6 knockdown under physiological conditions caused increased oxidative stress, apoptosis, and expression of pro-inflammatory cytokines.[2].
BI-3802 is potent and efficacious BCL6 inhibitor, inhibiting the BTB domain of BCL6, with an IC50 of ≤3 nM; BI-3802 has antitumor activity[3]. BI-3802 is a small molecule that binds to the Broad-complex, Tramtrack and Bric-à-brac (BTB) domain of the oncogenic transcription factor B cell lymphoma 6 (BCL6) and leads to the proteasomal degradation of BCL6. It induces polymerization coupled to highly specific protein degradation, which in the case of BCL6 leads to increased pharmacological activity compared to the effects induced by other BCL6 inhibitors[4].
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