Targeting BCL6 protein is an effective therapeutic approach for treating diffuse large B-cell lymphoma (DLBCL). 109, 110 BI-3802 (Table ) induces polymerization of BCL6 and interaction between BCL6 and SIAH1 E3 ligase. SIAH1 mediates ubiquitination and degradation of polymerized BCL6. 111, 112 SIAH1 recognizes VxP motif and exhibits minor affinity to BCL6. The binding affinity between polymerized BCL6 and SIAH1 is significantly enhanced. CCT369260 (Table ), an analogue of BI-3802 with improved physiochemical properties, has progressed into pharmacokinetic studies. The results show degradation of tumoral BCL6 in vivo following oral dosing in a lymphoma xenograft mouse model. 113