79-6 (CID5721353)

Small molecular BCL6 inhibitor 79-6 is a cell-permeable oxindole compound that selectively inhibits the transcriptional repression activity of BCL6 but does not affect BCL6 protein levels^[2]. 79-6 binds an aromatic pocket situated in the BTB domain lateral groove, induces disruption of BCL6 transcriptional complexes, reactivation of BCL6 target genes and selective killing of BCL6-dependent DLBCL cells^[1]. BCL6 can also interact with MTA3 through its RD2 domain and represses the terminal differentiation. It recruits CtBP through its DBD domain and represses its own expression. 79-6 suppresses invasive ability and colony-forming ability in both of MCF-7 and MDA231 cells. The inhibition of BCL6 with 79-6 enhanced the mRNA expression of E-cadherin in both of MCF-7 and MDA231 cells. 79-6 reverses the functions of BCL6 in the positive regulation of EMT, invasion and transcriptional repression of E-cadherin in breast cancer cells^[2].

Administration of 50 mg/kg/day 79-6 to SCID mice induced a 65-70% reduction in the size of established BCL6-dependent DLBCL xenografts, but had no effect on BCL6-independent DLBCLs^[1]. Therapeutic targeting of BCL6 with the small molecule 79-6 is an effective antilymphoma strategy in vivo^[3].

• Cell lines

  MCF-7 and MDA231 cells

• Concentrations

  200 μM

• Incubation Time

  48 h

• Method

  MCF-7 and MDA231 cells were plated on the upper chamber of the filters and were treated with vehicle (DMSO) or 79-6 (200 µmol/L) for 48 hours respectively. The cells invaded to the underside of the filter were counted (magnification, ×200).

• Animal Models

  SCID mice injected (s.c.) with BCL6-dependent DLBCL cell lines (OCI-Ly7 and SU-DHL6) to form tumors

• Dosages

  50 mg/kg

• Administration

  i.p.