FX1
目录号 : GC18169
A BCL6 inhibitor
Cas No.:1426138-42-2
Sample solution is provided at 25 µL, 10mM.
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FX1 is a potent and specific BCL6 inhibitor, with an IC50 of around 35 μM.
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[1].
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[1].
References:
[1]. Mariano G et al. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J Clin Invest. 2016 Sep 1; 126(9): 3351–3362.
Cell experiment: | Cell viability is determined with the fluorescent redox dye. Fluorescence is determined for 3 replicates per treatment condition or vehicle with the microplate reader. Cell viability of the drug-treated cells is normalized to their vehicle-treated controls, and the results are expressed as percentage viability. The drug effect as 100-percentage viability is calculated. Through dose-effect curves the drug concentration that inhibits the growth of cell lines by 50% compare with vehicle (GI50) is determined. Experiments are performed in triplicate. For combination treatments, cells are exposed to a dose curve of each drug alone or their combination in constant ratio, and cell viability is determined. To compare different schedules of treatments, the cells are treated in triplicate as follows: FX1 and doxorubicin simultaneously and cells treated for 48 hours; FX1 first and 24 hours after doxorubicin is added and treats for an extra 48 hours; doxorubicin first and 24 hours after FX1 is added and treats for an extra 48 hours. Then, the software is used to plot dose-effect curves and calculate the dose-reduction index[1]. |
Animal experiment: | Six-to 8-week-old male mice are injected s.c. with 107 low-passage human SUDHL-6, OCI-Ly7, or Toledo cells. Alternatively, 6-to 8-week-old mice are injected with low-passage HBL-1 cells. When tumors reach a palpable size (approximately 100 mm3), mice are assigned in a randomized way to treatment groups and treated i.p. with 25 or 50 mg/kg/d of the drugs (including FX1). Drugs are reconstituted in PEG-400 and stored at -20°C until use. Tumor size is measured 3 times a week with an electronic digital caliper in 2 dimensions, and then tumor volume is calculated[1]. |
References: [1]. Mariano G et al. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J Clin Invest. 2016 Sep 1; 126(9): 3351–3362. | |
| Cas No. | 1426138-42-2 | SDF | |
| 化学名 | (5Z)-5-(5-Chloro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)-4-oxo-2-thioxo-3-thiazolidinepropanoic acid | ||
| Canonical SMILES | O=C(O)CCN(C/1=O)C(SC1=C2C(NC3=C/2C=C(Cl)C=C3)=O)=S | ||
| 分子式 | C14H9ClN2O4S2 | 分子量 | 367.969 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: slightly soluble,PBS (pH 7.2): slightly soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7176 mL | 13.5881 mL | 27.1762 mL |
| 5 mM | 0.5435 mL | 2.7176 mL | 5.4352 mL |
| 10 mM | 0.2718 mL | 1.3588 mL | 2.7176 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet