CID-5721353 is an inhibitor of the transcriptional repressor B cell lymphoma 6 (Bcl-6; Ki = 147 μM). It is selective for Bcl-6 over Kaiso, hypermethylated in cancer 1 (HIC1), and promyelocytic leukemia zinc finger (PLZF) at 50 μM. CID-5721353 is cytotoxic against Bcl-6-dependent SU-DLH-6, SU-DLH-4, Farage, OCI-LY7, OCI-LY1, and OCI-LY10 diffuse large B cell lymphoma (DLBCL) cells (GI50s = 0.024-0.936 mM) but not Bcl-6-independent Toledo or OCI-LY4 DLBCL cells (GI50 = >15 mM for both). It increases expression of the Bcl-6 target genes ATR, TP53, CD69, p21, and CD44 in SU-DLH-6 and SU-DHL-4 cells when used at a concentration of 50 μM. CID-5721353 (50 mg/kg) reduces tumor growth in OCI-LY7 and SU-DHL-6 mouse xenograft models.
