FX1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、特异性的 BCL6 BTB 结构域抑制剂，Kd 为 7 uM，其结合亲和力比天然 BCL6 配体 SMRT (Kd=30 uM) 更高。

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.

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.

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.

FX-1 | FX 1 | BCL6 inhibitor FX1

Angiogenesis

Bcl-2

BCL-6

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1426138-42-2

368.806

C14H9ClN2O4S2

>98% (HPLC)

DMSO: 30 mg/mL, Need Ultrasonic （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(O)CCN(C/1=O)C(SC1=C2C(NC3=C/2C=C(Cl)C=C3)=O)=S

(Z)-3-(5-(5-chloro-2-oxoindolin-3-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)propanoic acid

(-20℃)

With Ice Pack

≥ 2 years