Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein-protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3,5)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2-benzo[]imidazol-2-one (CCT369260), which reduces BCL6 levels in a lymphoma xenograft mouse model following oral dosing.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184563 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.9b02076 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Primary diffuse large B-cell lymphoma of non-germinal center type with BCL-6 positivity in the kidney: A case report.
Int J Surg Case Rep
August 2025
Department of Urology, The Fourth Affiliated Hospital of Dali University, Chuxiong, Yunnan 675000, China. Electronic address:
Introduction And Importance: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, yet primary renal involvement is rare, constituting less than 1 % of renal malignancies. A case of non-germinal center B-cell-like (non-GCB) DLBCL with BCL-6 positivity is particularly unique. Conventionally, BCL-6 is linked to germinal center B-cell-like (GCB) subtypes.
View Article and Find Full Text PDFBcl6 reactivity is associated with a distinct immune landscape and spatial transcriptome in COVID-19.
JCI Insight
September 2025
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the acute stages of viral infection, remains poorly understood: We have analyzed lung-draining lymph nodes (LD-LNs) from COVID-19 autopsies using multiplex imaging and spatial transcriptomics to examine the immune landscape with respect to follicular immune reactivity. We identified three groups of donors based on the Bcl6 prevalence of their Reactive Follicles (RFs): RF-Bcl6no/low, RF-Bcl6int, and RF-Bcl6high. A distinct B/TFH immune landscape, associated with increased prevalence of proliferating B-cell and TFH-cell subsets, was found in RF-Bcl6high LD-LNs.
View Article and Find Full Text PDFCentral nervous system tumors with BCOR internal tandem duplications: a systematic review of clinical, radiological, and pathological features in 69 cases.
J Pathol Transl Med
September 2025
Department of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
Central nervous system tumors with BCL6 corepressor (BCOR) internal tandem duplications (ITDs) constitute a rare, recently characterized pediatric neoplasm with distinct molecular and histopathological features. To date, 69 cases have been documented in the literature, including our institutional case. These neoplasms predominantly occur in young children, with the cerebellum representing the most frequent anatomical location.
View Article and Find Full Text PDFHepatitis C virus modified E2-mRNA-LNP candidate vaccine promotes helper CXCR5T cells.
J Virol
September 2025
Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
T cells play an important role in initiating antibody responses by instructive signals of cell-cell contacts and secretion of soluble cytokines as mediators. We investigated the role of the modified soluble E2 (sE2) antigen from hepatitis C virus (HCV) on healthy human peripheral blood mononuclear cell (PBMC)-derived immune cells or immunized mouse cells to understand the mechanisms of immune regulation by the candidate vaccine antigen. HCV E2 and E2 displayed a role in inducing type 17 T-helper cell (Th17) phenotype, as indicated by interleukin-17 (IL-17) expression and signal transducer and activator of transcription 3 (Stat3) phosphorylation.
View Article and Find Full Text PDFUnlabelled: Currently approved type 1 diabetes (T1D) immunotherapies broadly target T cells and delay but do not fully prevent diabetes development, highlighting the need for more selective targets. Anti-insulin germinal center B cells are uniquely able to present pathogenic insulin epitopes and drive anti-insulin T cells to adopt a T follicular helper fate. T cell expression of BCL6, a key transcriptional repressor in the germinal center response, is essential for spontaneous diabetes in non-obese diabetic (NOD) mice.
View Article and Find Full Text PDF