T-5224
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
T-5224是一种新型的非肽类c-Fos/AP-1小分子抑制剂[1]。
在c-Fos/AP-1启动子-荧光素酶实验中，T-5224特异性的抑制c-Fos/AP-1，而不影响c-Fos蛋白家族成员本身的水平。此外，T-5224选择性地抑制c-Fos/c-Jun的DNA结合活性，而不影响其它转录因子（C/EBPα和ATF-2、MyoD、Sp-1和NF-κB/p65）的DNA结合活性。一些研究表明，T-5224有效抑制胶原诱导的关节炎（CIA）的发展。除此之外，T-5224抑制活化T细胞核因子（NFAT）的表达和核因子κB受体活化子配体（RANKL）诱导的巨噬细胞-破骨细胞前体RAW264.7细胞的破骨细胞生成。在IL-1β刺激的人滑膜SW982细胞中，T-5224还可以抑制介质（MMP-1、MMP-3、IL-6和TNF-α）的产生，IC50值约为10 μM。在体内药代动力学分析中，T-5224的ED50值约为1-10 mg/kg，Cmax值为0.03-0.5 μM[1]。
参考文献：
[1] Aikawa Y1, Morimoto K, Yamamoto T, Chaki H, Hashiramoto A, Narita H, Hirono S, Shiozawa S. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol. 2008 Jul;26(7):817-23.
- 1. Susumu Ohya, Miki Matsui, et al. "Downregulation of IL-8 and IL-10 by the Activation of Ca2+-Activated K+ Channel KCa3.1 in THP-1-Derived M2 Macrophages." Int J Mol Sci. 2022 Aug 3;23(15):8603. PMID: 35955737
- 2. Qian Zhao, Kaixin Zhang, et al. "OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein-1 inhibitor T-5224." Transl Oncol. 2021 Aug;14(8):101100. PMID: 33993098
- 3. Rengyun Liu, Jie Tan, et al. "Therapeutic targeting of FOS in mutant TERT cancers through removing TERT suppression of apoptosis via regulating survivin and TRAIL-R2." Proc Natl Acad Sci U S A. 2021 Mar 16;118(11):e2022779118. PMID: 33836600
- 4. Philipp Novoszel, Martin Holcmann, et al. "Psoriatic skin inflammation is promoted by c-Jun/AP-1-dependent CCL2 and IL-23 expression in dendritic cells." EMBO Mol Med. 2021 Apr 9;13(4):e12409. PMID: 33724710
- 5. Xinh-Xinh Nguyen, Tetsuya Nishimoto, et al. "Lysyl oxidase directly contributes to extracellular matrix production and fibrosis in systemic sclerosis." Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1):L29-L40. PMID: 33026236
- 6. Drummond RA, Swamydas M, et al. "CARD9(+) microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment." Nat Immunol. 2019 May;20(5):559-570. PMID: 30996332
- 7. Lv SY, Cui B, et al. "Spexin/NPQ Induces Fos and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model." Am J Pathol. 2019 Jan 19. pii:S0002-9440(18)30290-6. PMID: 30664863
- 8. Choi Y, Rosewell KL, et al. "FOS, a Critical Downstream Mediator of PGR and EGF-signaling Necessary for Ovulatory Prostaglandins in the Human Ovary." J Clin Endocrinol Metab. 2018 Aug 16. PMID: 30124866
- 9. Levi NJ, Wilson CW, et al. "Obesity-related cellular stressors regulate gonadotropin releasing hormone gene expression via c-Fos/AP-1." Mol Cell Endocrinol. 2018 Jul 29. pii: S0303-7207(18)30235-1. PMID: 30063946
- 10. Chih-Wei Chen. "WNT5A induziert über eine JNK-abhängige Aktivierung von latentem TGF-β Fibrose." Friedrich-Alexander-Universität Erlangen-ürnberg.2018/01/15.
- 11. Isha Dey, Neil A. Bradbury. "Activation of TPA-response element present in human Lemur Tyrosine Kinase 2 (lmtk2) gene increases its expression." Biochemistry and Biophysics Reports. 2017 September 21.
- 12. Shao YY, Hsieh MS, et al. "Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells." Oncotarget. 2017 Sep 30;8(49):86681-86692. PMID: 29156827
- 13. Jang B, Ishigami A, et al. "The Peptidylarginine Deiminase Inhibitor Cl-Amidine Suppresses Inducible Nitric Oxide Synthase Expression in Dendritic Cells." Int J Mol Sci. 2017 Oct 27;18(11). pii: E2258. PMID: 29077055
- 14. Johannessen L, Sundberg TB, et al. "Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells. "Nat Chem Biol. 2017 Oct;13(10):1102-1108. PMID: 28805801
- 15. Chen H, Qu J, et al. "Mechanosensing by the α6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis." Nat Commun. 2016 Aug 18;7:12564. PMID: 27535718
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 517.53 |
| Cas No. | 530141-72-1 |
| Formula | C29H27NO8 |
| Solubility | ≥25.88 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-oxo-2,3-dihydrobenzo[d]isoxazol-6-yl)methoxy)phenyl)propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | O=C1NOC2=CC(COC(C=CC(C(C3=C(O)C=C(OC4CCCC4)C=C3)=O)=C5)=C5CCC(O)=O)=CC=C12 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
|
抑制活性 |
使用TransAM试剂盒（Active Motif）测量转录因子的DNA结合活性。将含有诸如c-Fos/AP-1、c-Jun/AP-1、ATF-2、C/EBPa、MyoD、Sp-1或NF-kB/p65因子的核提取物和各种浓度的T-5224加入预先包被各自的共有双链（ds）DNA寡聚体的多孔板中。在孵育1小时后，根据实验protocol，通过使用对相应转录因子具有反应性的抗体检测与其各自的共有dsDNA序列结合的转录因子。 |
| 细胞实验: [1] | |
|
细胞系 |
人类滑膜SW982细胞，人软骨细胞SW1353细胞 |
|
制备方法 |
可溶于DMSO，若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
|
反应条件 |
0.1、1、10、100、1000 μM. |
|
实验结果 |
在由IL-1β刺激的人滑膜SW982细胞中，T-5224抑制MMP-1、MMP-3、IL-6和TNFα的生成。在IL-1β刺激的人软骨细胞SW1353细胞中，T-5224抑制MMP-3和MMP-13的生成，IC50值为10 μM。 |
| 动物实验: [1] | |
|
动物模型 |
II型胶原诱导的关节炎（CIA）雄性DBA/1J小鼠。 |
|
给药剂量 |
0.3、1、3、30 mg/kg，在关节炎发病前第21天每天一次，口服。 |
|
实验结果 |
在第50天，3和30 mg/kg T-5224分别抑制64％和91％的关节炎发展。30 mg/kg的T-5224抑制关节破坏，并完全保护关节不被破坏。在30 mg/kg剂量下，T-5224显著抑制MMP-2、MMP-3、MMP-9、MMP-13、IL-1β、IL-6和TNFα。 |
|
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
|
References: [1]. Aikawa Y, Morimoto K, Yamamoto T, et al. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol, 2008, 26(7): 817-823. |
|
质量控制和MSDS
- 批次:
化学结构
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
