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]