FX1

SKU: orb1226305

Description

A potent, specific BCL6 BTB domain inhibitor with Kd of 7 uM, binds with a greater affinity than the natural BCL6 ligand SMRT (Kd=30 uM); exhibits 10-fold greater inhibitory activity against the BCL6 BTB domain in reporter assays with IC50 of 35 uM, displays good selectivity against a panel of 50 different kinases; disrupts formation of the BCL6 repression complex, reactivates BCL6 target genes, suppresses ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo.

Key Properties

• CAS Number: 1426138-42-2
• MW: 368.806
• Purity: >98% (HPLC)
• Formula: C₁₄H₉ClN₂O₄S₂
• SMILES: O=C(O)CCN(C/1=O)C(SC1=C2C(NC3=C/2C=C(Cl)C=C3)=O)=S
• Target: Bcl-2
• Solubility: DMSO: 30 mg/mL, Need Ultrasonic （ < 1 mg/ml refers to the product slightly soluble or insoluble )

Bioactivity

• 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 compared with vehicle.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

FX-1 | FX 1 | BCL6 inhibitor FX1

Quick Database Links

Gene Symbol

Bcl-2