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FX1 is an inhibitor of the transcription factor B cell lymphoma 6 (BCL6; IC50 = ~35 μM).1 It is selective for BCL6 over a panel of 50 kinases at a concentration of 10 μM. FX1 (50 μM) reduces recruitment of the BCL6 corepressor proteins SMRT and BCOR to the BCL6 target loci CDKN1A, CD69, and CXCR4 in a ChIP assay. It represses growth of Farage, SU-DLH-6, DOHH-2, OCI-Ly7, RCK8, SU-DHL-4, OCI-Ly1, and SC-1 BCL6-dependent cell lines (GI50s = 16-54 μM) but not OCI-LY1-B50, Karpas 433, OCI-Ly19, or Toledo BCL6-independent cell lines (GI50s = >125 μM). In vivo, FX1 (50 mg/kg) reduces tumor volume in an HBL-1 large B cell lymphoma mouse xenograft model.
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1. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J. Clin. Invest. 126(9), 3351-3362 (2016).