2. Academic Validation
  3. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo

A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo

  • Cancer Cell. 2010 Apr 13;17(4):400-11. doi: 10.1016/j.ccr.2009.12.050.
Leandro C Cerchietti 1,  Alexandru F Ghetu,  Xiao Zhu,  Gustavo F Da Silva,  Shijun Zhong,  Marilyn Matthews,  Karen L Bunting,  Jose M Polo,  Christophe Farès,  Cheryl H Arrowsmith,  Shao Ning Yang,  Monica Garcia,  Andrew Coop,  Alexander D Mackerell Jr,  Gilbert G Privé,  Ari Melnick
Affiliations

Affiliation

  • 1 Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
PMID: 20385364 DOI: 10.1016/j.ccr.2009.12.050
Abstract

The BCL6 transcriptional repressor is the most frequently involved oncogene in diffuse large B cell lymphoma (DLBCL). We combined computer-aided drug design with functional assays to identify low-molecular-weight compounds that bind to the corepressor binding groove of the BCL6 BTB domain. One such compound disrupted BCL6/corepressor complexes in vitro and in vivo, and was observed by X-ray crystallography and NMR to bind the critical site within the BTB groove. This compound could induce expression of BCL6 target genes and kill BCL6-positive DLBCL cell lines. In xenotransplantation experiments, the compound was nontoxic and potently suppressed DLBCL tumors in vivo. The compound also killed primary DLBCLs from human patients.

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