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Purity: ≥98%
T-5224 is a novel and selective inhibitor of c-Fos/activator protein-1 (AP-1) which is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. T-5224 has potential use in cancer and rheumatoid arthritis therapy. T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice. T-5224 has been investigated in phase II human clinical trials. T-5224 (0-80 μM) significantly inhibits the invasion, migration, and MMP activity of HSC-3-M3 cells in a dose-dependent manner. T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.
| ln Vitro |
With a mean IC50 of roughly 10 μM, T-5224 inhibits the in-vitro production of the mediators MMP-1, MMP-3, IL-6, and TNF-α by IL-1β-stimulated human synovial SW982 cells[2]. In a dose-dependent manner, T- 5224 (0-80 μM) significantly inhibits the invasion, migration, and MMP activity of HSC-3-M3 cells[3].
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| ln Vivo |
After intraperitoneal injection of LPS, administration of T-5224 (300 mg/kg, po) reduces the lethality (27%) and provides significant protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST, and MIP-1α and MCP-1 in liver tissue[4]. It is possible that G2 is not a metabolite that is unique to humans because it is found in rat and monkey liver microsomes as a major metabolite of T-5224[5]. In C57BL/6 mice, T-5224 (300 mg/kg, po) suppresses the synthesis of TNF-alpha and other downstream effectors[6].
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| References |
[1]. Makino H, et al. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebraldisc degeneration and associated pain. Sci Rep. 2017 Dec 5;7(1):16983.
[2]. Aikawa Y, et al. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol. 2008 Jul;26(7):817-23. [3]. Kamide D, et al. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci.?2016 May;107(5):666-73. [4]. Izuta S, et al. T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice. Biotechnol Lett. 2012 Dec;34(12):2175-82. [5]. Uchihashi S, et al. Metabolism of the c-Fos/activator protein-1 inhibitor T-5224 by multiple human UDP-glucuronosyltransferase isoforms. Drug Metab Dispos. 2011 May;39(5):803-13. [6]. Miyazaki H, et al. The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin-induced acute kidney injury in mice. BMC Nephrol. 2012 Nov 23;13:153 |
| Molecular Formula |
C29H27NO8
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| Molecular Weight |
517.53
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| CAS # |
530141-72-1
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| SMILES |
O=C(O)CCC1=CC(C(C2=CC=C(OC3CCCC3)C=C2O)=O)=CC=C1OCC4=CC5=C(C=C4)C(O)=NO5
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (9.66 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (9.66 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Effect of T‐5224 on tumor cell proliferationin vitro.Cancer Sci.2016 May;107(5):666-73. |
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 Protocol and results ofin vivostudy using an orthotopic model of head and neck squamous cell carcinoma.
Morphological changes in tumor cells (HSC‐3‐M3 head and neck squamous cell carcinoma) after replacement with normal or T‐5224 (+) media.Cancer Sci.2016 May;107(5):666-73. |
 Effect of T‐5224 on the transcription and activity of MMP‐2 and ‐9.
Effect of T‐5224 on the invasion activity of HSC‐3‐M3 head and neck squamous cell carcinoma cells.Cancer Sci.2016 May;107(5):666-73. |
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