| Bioactivity | T-5224 is a transcription factor c-Fos/activator protein (AP)-1 inhibitor with anti-inflammatory effects, which specifically inhibits the DNA binding activity of c-Fos/c-Jun without affecting other transcription factors. T-5224 inhibits the IL-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription[1][2]. | ||||||||||||
| Target | c-Fos/activator protein (AP)-1 | ||||||||||||
| Invitro | T-5224 inhibits in-vitro production of the mediators MMP-1, MMP-3, IL-6 and TNF-α by IL-1β-stimulated human synovial SW982 cells with the mean IC50 of about 10 μM[2].T-5224 (0-80 μM) significantly inhibits the invasion, migration, and MMP activity of HSC-3-M3 cells in a dose-dependent manner[3]. | ||||||||||||
| In Vivo | Administration of T-5224 (300 mg/kg, p.o.) after intraperitoneal injection of LPS impartes appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduces the lethality (27%)[4].G2 is observed in rat and monkey liver microsomes as a major metabolite of T-5224, suggesting that G2 is not a human-specific metabolite[5].T-5224 (300 mg/kg, p.o.) inhibits the production of TNF-alpha and other downstream effectors in C57BL/6 mice[6]. | ||||||||||||
| Name | T-5224 | ||||||||||||
| CAS | 530141-72-1 | ||||||||||||
| Formula | C29H27NO8 | ||||||||||||
| Molar Mass | 517.53 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |