inS3-54A18
目录号 : GC32862
inS3-54A18 is a potent inhibitor of STAT3 with anti-cancer properties.
Cas No.:328998-53-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Briefly, 5×106 A549 cells are injected subcutaneously in the flanks of 5-6-week-old male NOD/SCID mice. When the tumor volume reach about 50.0 mm3, the mice are randomized using online program into two different groups (6/group) with one group treated by formulation vehicle control and the other by A18 at 200 mg/kg with oral dosing 2-3 times a week for 4 weeks. One mouse in each group dies during the study and is eliminated. Tumor volume and body weight of the remaining five mice in each group are measured twice a week without blinding. On the thirty-fifth day after implant, mice are euthanized and the tumor tissues are harvested and weighed. Necropsy is also performed to determine changes in the heart, lungs, kidneys, liver and spleen. |
References: [1]. Huang W, et al. Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo. Oncogene. 2016 Feb 11;35(6):783-92 | |
inS3-54A18 is a potent inhibitor of STAT3 with anti-cancer properties.
[1] Huang W, et al. Oncogene. 2016 Feb 11;35(6):783-92. doi: 10.1038/onc.2015.215.
| Cas No. | 328998-53-4 | SDF | |
| Canonical SMILES | O=C1N(C2=CC=C(O)C=C2)C(C3=CC=CC=C3)=C/C1=C/C4=CC=C(Cl)C=C4 | ||
| 分子式 | C23H16ClNO2 | 分子量 | 373.83 |
| 溶解度 | DMSO : ≥ 150 mg/mL (401.25 mM) | 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 | 2.675 mL | 13.3751 mL | 26.7501 mL |
| 5 mM | 0.535 mL | 2.675 mL | 5.35 mL |
| 10 mM | 0.2675 mL | 1.3375 mL | 2.675 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。
Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo
Oncogene 2016 Feb 11;35(6):783-92.PMID:26073084DOI:10.1038/onc.2015.215
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 promises to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its 'undruggable' nature and potentially limited selectivity. In a previous study, we reported an improved in silico approach targeting the DBD of STAT3 that resulted in a small-molecule STAT3 inhibitor (inS3-54). Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1. In this study, we describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound (inS3-54A18) with increased specificity and pharmacological properties. inS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. inS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Thus inS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics targeting the DBD of human STAT3 and DBD of transcription factors may not be 'undruggable' as previously thought.