SH-4-54
目录号 : GC14658
SH-4-54 是一种特异性 STAT3 抑制剂，KD为 300 nM。通常用于研究胶质母细胞瘤等脑癌的治疗。
Cas No.:1456632-40-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
SH-4-54 is a specific STAT3 inhibitor with a KD of 300 nM[1]. It is commonly used in the study of treatments for brain cancers such as glioblastoma[2-3].
SH-4-54 demonstrates potent cytotoxic effects on tumor cells with aberrantly active STAT3, exhibiting an IC50 range of 1.0-2.7μM for glioma U251MG and U87MG cells[3]. SH-4-54 (16μM; 72h) effectively induces apoptosis in temozolomide-resistant glioblastoma multiforme cells by mitoSTAT3 pathway, leading to disrupted oxidative phosphorylation and negative regulation of mitochondrial-encoded genes[4]. In addition, SH-4-54 reduces cell survival and phosphorylated STAT3 levels in various tumors, including bladder cancer and pancreatic cancer[5-6].
SH-4-54 (6 mg/kg; every 2 or 3 days; intravenous administration) effectively blocked the DNA binding activity of STAT3, leading to the inhibition of STAT3-dependent gene transcription in human glioma, breast, and prostate cancer cells, as well as in v-Src-transformed murine fibroblasts. And effectively suppressed tumor growth in mouse xenograft models of glioma and breast cancer [3].
References:
[1]. Haftchenary S, Luchman HA, Jouk AO, et al. Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma. ACS Med Chem Lett. 2013 Sep 8;4(11):1102-7.
[2]. Yu D, Wang S, Wang J, et al. EZH2-STAT3 signaling pathway regulates GSDMD-mediated pyroptosis in glioblastoma. Cell Death Discov. 2024 Jul 28;10(1):341.
[3]. Yue P, Lopez-Tapia F, Paladino D, et al. Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer Res. 2016 Feb 1;76(3):652-63.
[4]. Cui P, Wei F, Hou J, et al. STAT3 inhibition induced temozolomide-resistant glioblastoma apoptosis via triggering mitochondrial STAT3 translocation and respiratory chain dysfunction. Cell Signal. 2020 Jul;71:109598.
[5]. Hindupur SV, Schmid SC, Koch JA, et al. STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy. Int J Mol Sci. 2020 Feb 7;21(3):1106.
[6]. Arpin CC, Mac S, Jiang Y, et al. Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics. Mol Cancer Ther. 2016 May;15(5):794-805.
SH-4-54 是一种特异性 STAT3 抑制剂，KD为 300 nM[1]。通常用于研究胶质母细胞瘤等脑癌的治疗[2-3]。
SH-4-54 对于 STAT3 异常活跃的肿瘤细胞表现出强大的细胞毒性，其对胶质瘤 U251MG 和 U87MG 细胞的 IC50 范围为 1.0-2.7 μM[3]。SH-4-54 (16μM; 72h) 通过 mitoSTAT3 通路有效诱导耐替莫唑胺的多形性胶质母细胞瘤细胞凋亡，导致氧化磷酸化受损及线粒体编码基因的负调控[4]。此外，SH-4-54 在多种肿瘤中（包括膀胱癌、胰腺癌）降低细胞存活率和磷酸化的 STAT3 水平，促进细胞凋亡[5-6]。
SH-4-54（6mg/kg; every 2 or 3 days; intravenous administration）有效阻断了STAT3的DNA结合活性，导致人类胶质瘤、乳腺癌和前列腺癌细胞以及v-Src转化的小鼠成纤维细胞中STAT3依赖的基因转录被抑制，在小鼠异种移植模型中有效抑制了胶质瘤和乳腺癌的肿瘤生长[3]。
| Cell experiment [1]: | |
Cell lines | U251MG; U87MG |
Preparation Method | Cells were cultured in Roswell Park Memorial Institute medium-1640 supplemented with 1% nonessential amino acids and 10% heat-inactivated fetal bovine serum. Cells in 96-well plates were treated with either SH-4-54 or a vehicle control for 72 hours, after which they were subjected to a CyQuant cell proliferation assay. Alternatively, cells were harvested, and viable cells were counted using trypan blue exclusion and phase contrast microscopy. |
Reaction Conditions | 0-10 μM ; 72 hours |
Applications | SH-4-54 exhibits potent cytotoxic effects against malignant cells harboring aberrantly active Stat3. |
| Animal experiment [2]: | |
Animal models | NOD-SCID mice (Glioma model) |
Preparation Method | NOD-SCID mice were orthotopically xenografted with 105 BT73 glioma cells. Starting on day 7, the mice received intraperitoneal injections of 10 mg/kg of SH-4-54 or vehicle control on a schedule of 4 days on followed by 3 days off. Animals were sacrificed 2 hours after the last dose, and brain tumors were extracted for immunohistochemical analysis of pSTAT3, Ki67 (proliferation), and TUNEL (apoptosis). |
Dosage form | 10 mg/kg; 4 days on/3 days off; i.p. |
Applications | SH-4-54 reduced pSTAT3 expression in tumor cells and decreased proliferation while increasing apoptosis in treated tumors. |
References: | |
| Cas No. | 1456632-40-8 | SDF | |
| Canonical SMILES | FC(C(S(=O)(N(C)CC(N(C1=CC=C(C(O)=O)C=C1)CC2=CC=C(C=C2)C3CCCCC3)=O)=O)=C(C(F)=C4F)F)=C4F | ||
| 分子式 | C29H27F5N2O5S | 分子量 | 610.59 |
| 溶解度 | ≥ 20.25mg/mL in DMSO | 储存条件 | Desiccate 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6378 mL | 8.1888 mL | 16.3776 mL |
| 5 mM | 0.3276 mL | 1.6378 mL | 3.2755 mL |
| 10 mM | 0.1638 mL | 0.8189 mL | 1.6378 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet