|Title||Progress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Ai, Y, Hwang, L, Mackerell, AD, Melnick, A, Xue, F|
|Journal||J Med Chem|
|Date Published||2021 Apr 22|
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.
|Alternate Journal||J Med Chem|