bcl6-in-3

BCL6-IN-3 is a potent BCL6 inhibitor with GI50 of 70 nM in SU-DHL4 cells. BCL6-in-3 regulates cell activation, differentiation, DNA damage and apoptosis, and has antitumor activity.

EN171, a covalent ligand, selectively binds to C38 and C96 on 14-3-3, intensifying 14-3-3's interactions with ERα, YAP, and TAZ. This action impairs both estrogen receptor and Hippo pathway transcriptional activities. Beyond serving as a molecular glue to augment native protein interactions, EN171 also functions as a covalent recruiter for 14-3-3 in heterobifunctional molecules. This facilitates the sequestration of nuclear neo-substrates, such as BRD4 and BLC6, into the cytosol.

BI-3802, a highly potent BCL6 degrader, targets and inhibits the Bric-à-brac (BTB) domain of BCL6, exhibiting an IC50 value of ≤3 nM. It induces polymerization of BCL6 and facilitates its degradation in a manner dependent on the E3 ligase SIAH1, demonstrating notable antitumor activity[1][2].