BCL6 INHIBITORS AS ANTICANCER AGENTS

摘要

The invention provides compositions and methods for blocking the BCL6 BTB domain with small molecule, non-peptide compounds as disclosed and claimed herein. BCL6 is a transcriptional repressor of the BTB-POZ (bric a brac, tramtrack, broad complex / pox virus zinc finger) family of proteins. It is required for normal development of germinal center (GC) B-cells and is also the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs), and constitutive expression of BCL6 in GC B-cells causes DLBCL in mice. DLBCLs are aggressive tumors that arise from germinal center (GC) B- cells and are the most common form of non-Hodgkin's lymphomas. BCL6 is required for survival of DLBCL cells and can limit their ability to respond to DNA damaging agents. It is also frequently expressed in follicular lymphomas (FLs), and may be required for survival of these tumors as well. DLBCL and FL collectively constitute ∼60-70% of B-cell lymphomas and the incidence of these tumors has been rising in recent decades.