T-5224
目录号 : GC16165
T-5224 是一种非肽类小分子 AP-1 抑制剂，特异性抑制 AP-1 与启动子区 AP-1 结合位点的结合，最初开发为抗炎药用于治疗类风湿性关节炎 (RA) 抑制炎症细胞因子和 MMPs 而没有任何副作用。
Cas No.:530141-72-1
Sample solution is provided at 25 µL, 10mM.
T-5224 is a non-peptidic small molecule AP-1 inhibitor that specifically inhibits the binding of AP-1 to the AP-1 binding site of the promoter region and was originally developed as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) suppressing inflammatory cytokines and MMPs without any side-effects.[1]
In vitro study indicated that transcriptional inhibition of the expression of MMPs by T-5224 is not limited to tumor cells only; it also occurs in the ECM of the surrounding tissue, and consequently, inhibits tumor cells from infiltrating the surrounding tissue. In addition, T-5224 potently inhibits the essential steps of metastasis, infiltration through the basement membrane barrier and migration into the ECM, by transcriptionally suppressing the expression of MMP-2 and -9.[1]
In vivo experiments demonstrated that T-5224 blocked serum TNF-α, HMGB-1, BUN, and creatinine concentrations, reducing mortality of LPS-induced AKI. These findings suggest that T-5224 may be protective against lethal LPS-induced AKI. T-5224 attenuated LPS-induced liver injury in mice. T-5224 may have beneficial effects in sepsis-induced organ dysfunctions. [3]
References:
[1]. Daisuke K. et al. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016 May; 107 (5) 666–673.
[2]. Mari I. et al. T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model. Journal of Intensive Care (2015) 3:49.
T-5224 是一种非肽类小分子 AP-1 抑制剂，特异性抑制 AP-1 与启动子区 AP-1 结合位点的结合，最初开发为抗炎药用于治疗类风湿性关节炎 (RA) 抑制炎症细胞因子和 MMPs 而没有任何副作用。[1]
体外研究表明，T-5224 对 MMP 表达的转录抑制不仅限于肿瘤细胞；它也发生在周围组织的 ECM 中，因此抑制肿瘤细胞浸润周围组织。此外，T-5224 通过转录抑制 MMP-2 和 -9 的表达，有效抑制转移、通过基底膜屏障浸润和迁移到 ECM 的基本步骤。[1]/p>\n
体内实验表明，T-5224 可阻断血清 TNF-α、HMGB-1、BUN 和肌酐浓度，降低 LPS 诱导的 AKI 的死亡率。这些发现表明 T-5224 可能对致命的 LPS 诱导的 AKI 具有保护作用。 T-5224 减轻 LPS 诱导的小鼠肝损伤。 T-5224 可能对败血症引起的器官功能障碍有益。 [3]
体内实验表明，T-5224 可阻断血清 TNF-α、HMGB-1、BUN 和肌酐浓度，降低 LPS 诱导的 AKI 的死亡率。这些发现表明 T-5224 可能对致命的 LPS 诱导的 AKI 具有保护作用。 T-5224 减轻 LPS 诱导的小鼠肝损伤。 T-5224 可能对败血症引起的器官功能障碍有益。 [3]
| Cell experiment [1]: | |
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Cell lines |
Human oral squamous carcinoma cell lines, OSC-19 and HSC-3-M3. |
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Preparation Method |
Cells were grown in DMEM supplemented with 10% FBS and penicillin (50 units ⁄ mL) ⁄ streptomycin (50 μg ⁄ mL) in a humidified atmosphere (5% CO2) at 37°C. T-5224 was dissolved in DMSO and diluted in culture medium to the target concentration for each experiment. For oral gavage administration, T-5224 was dissolved in polyvinylpyrrolidone (PVP) solution according to the manufacturer’s recommended procedure. |
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Reaction Conditions |
Cells were incubated in T-5224 (0–80 μM), and cell counts were carried out at 24, 48, and 72 h after treatment. |
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Applications |
T-5224 treatment could inhibit the invasion activity of highly metastatic tumor cell line HSC-3-M3. Cell migration was potently inhibited by T-5224 in both cell lines in a dose-dependent manner. Migration activity was almost completely inhibited in the medium containing 80 μM T-5224. |
| Animal experiment [1]: | |
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Animal models |
Female 5–7-week-old BALB⁄ c mice |
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Preparation Method |
HSC-3-M3 (1 x 105 cells) were suspended in 50 μL Hank’s Balanced Salts Solution and injected in the flank of the tongue at day 0. T-5224 was diluted in PVP solution, and T-5224 was given orally to the mice of the treatment group every day from day 1 for 4 weeks. |
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Dosage form |
150 mg⁄ kg |
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Applications |
T-5224 showed significant inhibitory effects against lymph node metastasis in the animal model of HNSCC. The rate of positive metastasis was significantly lower by T-5224 treatment. It is possible that higher doses (150 mg/kg) might be required for cells in which activity of AP-1 is intensively and constitutively activated by genetic mutations or substantial inflammation. |
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References: [1]. Daisuke K. et al. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016 May; 107 (5) 666–673. |
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| Cas No. | 530141-72-1 | SDF | |
| 化学名 | 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-oxo-2,3-dihydrobenzo[d]isoxazol-6-yl)methoxy)phenyl)propanoic acid | ||
| Canonical SMILES | O=C1NOC2=CC(COC(C=CC(C(C3=C(O)C=C(OC4CCCC4)C=C3)=O)=C5)=C5CCC(O)=O)=CC=C12 | ||
| 分子式 | C29H27NO8 | 分子量 | 517.53 |
| 溶解度 | ≥ 25.88mg/mL in DMSO | 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 | 1.9323 mL | 9.6613 mL | 19.3226 mL |
| 5 mM | 0.3865 mL | 1.9323 mL | 3.8645 mL |
| 10 mM | 0.1932 mL | 0.9661 mL | 1.9323 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
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Related Biological Data
Knockdown of AP-1 subunits caused the downregulation of TGFB1. (G) The effects of blocking the NF-κB and AP-1 signaling pathways on the expression of TGFB1.
Cells were treated with two NF-κB inhibitors, TPCA1, and BOT-64, and two AP-1 inhibitors, T-5224 (50µM, GLPBIO, Montclair, CA, USA, #GC16165) and SR11302 for 4h and then stimulated with 50ng/mL recombinant IL-1β for 2h.
Int J Biol Sci 16.2 (2020): 204. PMID: 31929749 IF: 6.58 -
Related Biological Data
EML4-ALK fusion protein regulates TF expression through pERK1/2/AP-1 pathway in H2228 cells. (C1-4) Pretreating H2228 cells with AP-1 inhibitor (T-5224, 400μm/L) also attenuated TF expression compared with DMSO control both at RNA (n=6) and protein level (n=3). Data are presented as means±SEM.
H2228 cells were Pretreated with T-5224 (GLPBIO, USA, 400μm/L).
J Thromb Thrombolys, 2023: 1-15. PMID: 37940761 IF: 4