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FX1

CAS No. : 1426138-42-2

產(chǎn)品活性：FX1 is a potent and specific BCL6 inhibitor, with an IC₅₀ of around 35 μM.

研究領(lǐng)域：Apoptosis

作用靶點：Bcl-2 Family  |  Apoptosis

In Vitro: DLBCL cells are exposed to 50 μM FX1 for 30 minutes. FX1 profoundly reduces recruitment of BCOR and SMRT to all 3 BCL6 target genes, but not at a negative control locus. There is little presence of SMRT at these loci in the BCL6-negative DLBCL cell line, which is not affected by FX1. The superior potency of FX1 versus 79-6 in disrupting BCL6 binding to SMRT is evident when these small molecules are compared head to head in quantitative ChIP assays in DLBCL cells after treatment with 50 μM FX1 for 6 hours. DLBCL cells are exposed to FX1 and mRNA is collect at 4 serial time points. FX1 almost invariantly induces significant derepression of these genes as compare with vehicle in 2 independent DLBCL cell lines.

In Vivo: Spleens in FX1-treating mice are macroscopically indistinguishable from vehicle controls. Total B cell abundance measured by flow cytometry is unaffected by FX1. GC B cells (GL7⁺FAS⁺B220⁺) are significantly depleted by exposure to FX1. Splenic architecture is examined by IHC. Staining with B220 antibody reveals normal B cell follicular structures, whereas staining for the GC B cell-specific marker peanut agglutinin shows profound loss of GCs. The half-life is estimated to be approximately 12 hours. Finally, whether FX1 can induce toxic effects in mice is assessed. No signs of toxicity, inflammation, or infection are evident from H&E-stained sections of lung, gastrointestinal tract, heart, kidney, liver, spleen, and bone marrow of the fixed organs from mice treated with FX1 compare with vehicle.

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