Progress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond.

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TitleProgress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond.
Publication TypeJournal Article
Year of Publication2021
AuthorsAi, Y, Hwang, L, Mackerell, AD, Melnick, A, Xue, F
JournalJ Med Chem
Volume64
Issue8
Pagination4333-4358
Date Published2021 Apr 22
ISSN1520-4804
Abstract

B-cell lymphoma 6 (BCL6) is a master regulator of germinal center formation that produce antibody-secreting plasma cells and memory B-cells for sustained immune responses. The BTB domain of BCL6 (BCL6) forms a homodimer that mediates transcriptional repression by recruiting its corepressor proteins to form a biologically functional transcriptional complex. The protein-protein interaction (PPI) between the BCL6 and its corepressors has emerged as a therapeutic target for the treatment of DLBCL and a number of other human cancers. This Perspective provides an overview of recent advances in the development of BCL6 inhibitors from reversible inhibitors, irreversible inhibitors, to BCL6 degraders. Inhibitor design and medicinal chemistry strategies for the development of novel compounds will be provided. The binding mode of new inhibitors to BCL6 are highlighted. Also, the and assays used for the evaluation of new compounds will be discussed.

DOI10.1021/acs.jmedchem.0c01686
Alternate JournalJ Med Chem
PubMed ID33844535