SB525334
(Synonyms: 6-[2-(1,1-二甲基乙基)-5-(6-甲基-2-吡啶基)-1H-咪唑-4-基]喹喔啉) 目录号 : GC14349
SB525334已被鉴定为一种高效且选择性的转化生长因子β1（TGF-β1）受体、活化素受体样激酶（ALK5）抑制剂。SB525334对ALK5激酶活性的IC50为14.3nM。
Cas No.:356559-20-1
Sample solution is provided at 25 µL, 10mM.
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SB525334 has been characterized as a potent and selective inhibitor of the transforming growth factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). SB525334 inhibited ALK5 kinase activity with an IC50 of 14.3nM [1].
In vitro, SB525334 (1μM; 16h) effectively attenuated the TGF-β1-induced epithelial to mesenchymal transition (EMT) in HPMCs[2]. In the presence of TGF-β, treatment of 4T1 tumor cells with SB525334 can reverse the pro-metastatic effect of TGF-β[3]. SB525334 (0, 1.25, 2.5, 5 and 10μM; 72h) can reduce gemcitabine resistance in resistant cells (MiaPaCa2 and AsPC1). Additionally, treatment with SB525334 (20μM; 24h) reduced the activity of the AKT signaling pathway, which plays a crucial role in gemcitabine resistance[4].
In vivo, In a mouse model of peritoneal fibrosis, cotreatment with chlorhexidine gluconate (CG) and SB525334 (20mg/kg/day; 28 days; p.o.) improved peritoneal thickness and fibrosis and restored peritoneal function[2]. In a orthotopic metastasis model, administration of SB525334(1mg/kg, 5mg/kg and 10mg/kg/every other day; 28 days; i.v.) significantly unleashed the antitumor response of infiltrating neutrophils[3].
References:
[1] Grygielko ET, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, Laping NJ. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005 Jun;313(3):943-51.
[2] Heo JY, Do JY, Lho Y, Kim AY, Kim SW, Kang SH. TGF-β1 Receptor Inhibitor SB525334 Attenuates the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells via the TGF-β1 Signaling Pathway. Biomedicines. 2021 Jul 19;9(7):839.
[3] Li Y, Hu Q, Li W, Liu S, Li K, Li X, Du J, Yu Z, Wang C, Zhang C. Simultaneous blockage of contextual TGF-β by cyto-pharmaceuticals to suppress breast cancer metastasis. J Control Release. 2021 Aug 10;336:40-53.
[4] Kim YJ, Hwang JS, Hong YB, Bae I, Seong YS. Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine. Anticancer Res. 2012 Mar;32(3):799-806.
SB525334已被鉴定为一种高效且选择性的转化生长因子β1（TGF-β1）受体、活化素受体样激酶（ALK5）抑制剂。SB525334对ALK5激酶活性的IC50为14.3nM[1]。
在体外实验中，SB525334（1μM; 16h）有效减轻了TGF-β1诱导的腹膜间皮细胞（HPMCs）的上皮-间充质转化（EMT）[2]。在TGF-β存在时，用SB525334处理4T1肿瘤细胞，可逆转TGF-β的促转移作用[3]。SB525334（0, 1.25, 2.5, 5和10μM; 72h）能够降低耐药细胞（MiaPaCa2和AsPC1）对吉西他滨的耐药性。此外，SB525334（20μM; 24h）的处理降低了AKT信号通路的活性，而该通路在吉西他滨耐药中起着关键作用[4]。
在体内实验中，在腹膜纤维化小鼠模型中，联合使用氯己定葡萄糖酸盐（CG）和SB525334（20mg/kg/天; 28天; 口服）能够改善腹膜厚度和纤维化，并恢复腹膜功能[2]。在乳腺癌原位转移模型中，SB525334（1mg/kg, 5mg/kg和10mg/kg/每隔一天给药; 28天; 静脉注射）的给药显著增强了浸润性中性粒细胞的抗肿瘤反应[3]。
| Cell experiment [1]: | |
Cell lines | HPMCs |
Preparation Method | The cytotoxicity of SB525334 was evaluated using the MTT assay. Approximately, 104 HPMCs/well were initially seeded and cultured in 96-well plates for 24h, then treated with SB525334 (0, 0.1, 1, 10, 100 and 200μM) in 200μL media for 24-72h. At the end of the incubation period, 20μL of MTT (5mg/mL) was added to each well and incubated at 37°C for 3.5h. Subsequently, 200μL of DMSO was added to each well to solubilize the formazan products. Absorbance was measured at 570nm using a microplate reader. |
Reaction Conditions | 0, 0.1, 1, 10, 100 and 200μM; 24-72h |
Applications | SB525334 exhibited no significant toxicity at concentrations up to 10μM, but displayed marked toxicity at 100μM. |
| Animal experiment [2]: | |
Animal models | female BALB/c mice |
Preparation Method | For orthotopic metastasis, 1×106 4T1 cells or 4T1-Luc cells suspended in 100μL PBS were injected into the right mammary fat pad of female BALB/c mice (6-8 weeks), and the lung metastasis was monitored by the IVIS Spectrum In Vivo Imaging System. Mice bearing 4T1 spontaneous lung metastasis were randomly divided into four groups receiving i.v. injection of saline and SB525334 at the dosage of 1mg/kg, 5mg/kg and 10mg/kg every other day. On day 28, the mice were sacrificed, and the harvested lungs were subjected to the H&E staining analysis to determine the metastasis-inhibiting efficacy. |
Dosage form | 1mg/kg, 5mg/kg, and 10mg/kg every other day; 28 days; i.v. |
Applications | In a orthotopic metastasis model, administration of SB525334 significantly unleashed the antitumor response of infiltrating neutrophils. |
References: | |
| Cas No. | 356559-20-1 | SDF | |
| 别名 | 6-[2-(1,1-二甲基乙基)-5-(6-甲基-2-吡啶基)-1H-咪唑-4-基]喹喔啉 | ||
| 化学名 | 6-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]quinoxaline | ||
| Canonical SMILES | CC1=CC=CC(=N1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=NC=CN=C4C=C3 | ||
| 分子式 | C21H21N5 | 分子量 | 343.42 |
| 溶解度 | ≥ 34.3mg/mL in DMSO, ≥ 23.8 mg/mL in EtOH | 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 | 2.9119 mL | 14.5594 mL | 29.1189 mL |
| 5 mM | 0.5824 mL | 2.9119 mL | 5.8238 mL |
| 10 mM | 0.2912 mL | 1.4559 mL | 2.9119 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