Open Access
ARTICLE
Novel Small Molecule DZ-865B Effectively Degrades BCL6, Promotes Apoptosis and Reduces Proliferation of Diffuse Large B-Cell Lymphoma Cells
Yanfeng Wang1,2,#, Xinyi Chen1,2,#, Yichen Yin1,2, Tao Li3,*, Jing Chen1,2,*
1 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
2 Key Laboratory of Fertility Maintenance Ministry of Education, Ningxia Medical University, Yinchuan, China
3 Department of Oncology, General Hospital of the Ningxia Medical University, Yinchuan, China
* Corresponding Author: Tao Li. Email: 
; Jing Chen. Email: 
# These authors contributed equally to this work
Oncology Research https://doi.org/10.32604/or.2026.068695
Received 04 June 2025; Accepted 04 January 2026; Published online 26 January 2026
Abstract
Objectives: B-cell lymphoma 6 (BCL6) is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma (DLBCL), making it a promising therapeutic target. This study aims to identify a novel small molecule, synthesized via proteolysis-targeting chimeras (PROTACs), capable of degrading BCL6, thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies. Methods: The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. Western blotting assays confirmed BCL6 expression in tumor cell lines, leading to the identification of the small molecule compound DZ-865B. To evaluate DZ-865B’s in vitro efficacy, multiple assays were performed, including protein immunoblotting, immunofluorescence, reverse transcription quantitative PCR, EDU proliferation, and soft agar cloning assays. Results: TCGA analysis revealed significant overexpression of BCL6 in DLBCL (p < 0.05), corroborated by immunohistological staining and western blotting. DZ-865B induced BCL6 degradation in DLBCL cell lines (OCI-LY-1 and SU-DHL-4) in a concentration- and time-dependent manner, and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway. Notably, DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression, leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis, effectively suppressing DLBCL cell growth. Conclusion: This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells, promoting apoptosis and inhibiting cellular proliferation. These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
Keywords
Diffuse large B-cell lymphoma (DLBCL); B-cell lymphoma 6 (BCL6); proteolysis-targeting chimeras (PROTACs); proliferation
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