T-5224

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]. IC50 & Target:c-Fos/activator protein (AP)-1^[1] In Vitro: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].