CCT369260

CCT369260 is a small-molecule benzimidazolone-based chemical probe that functions as a molecular glue degrader and inhibitor of the transcriptional repressor B-cell lymphoma 6 (BCL6), an oncogenic driver in diffuse large B-cell lymphoma and other lymphoid malignancies. It binds to the BTB domain at the BCL6 homodimer interface, stabilizing a higher-order protein complex that leads to selective proteasomal degradation of BCL6 and disruption of its interaction with corepressor proteins, resulting in antiproliferative and antitumor activity in BCL6-dependent lymphoma models. Developed by the Cancer Research UK Cancer Therapeutics Unit, CCT369260 is orally active, depletes tumoral BCL6 in vivo in lymphoma xenograft mouse models, but has high unbound clearance and modest oral bioavailability that limit its utility for sustained dosing and led to subsequent optimization into next-generation BCL6 degraders.

Other names

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