| 名称 | T-5224 |
| 描述 | T-5224 is a selective inhibitor of the transcription factor c-Fos/activator protein (AP)-1 with anti-inflammatory effects. T-5224 specifically suppresses the DNA-binding activity of c-Fos/c-Jun, thereby inhibiting IL-1β-induced transcriptional upregulation of Mmp-3, Mmp-13, and Adamts-5, without affecting the binding activity of other transcription factors. T-5224 can be used in research on rheumatoid arthritis, osteoarthritis, and cartilage degeneration. |
| 细胞实验 | NIH/3T3 cells were transiently transfected with the luciferase reporter plasmids pAP-1-Luc (× 7 TGACTAA), pNF-kB-Luc (× 5 TGGGGACTTTCCGC) or control phRL-TK, and cultured overnight. Cells were incubated in 0.5% FBS/DMEM containing T-5224 for 1 h, and then stimulated with PMA (10 ng/ml) or TNFa (10 ng/ml), and then cultured for 3 h, followed by measurement of lysate by using dual-luciferase reporter assay system [1]. |
| 激酶实验 | The DNA binding activity of transcription factors was measured using the TransAM kits. Nuclear extracts containing factors such as c-Fos/AP-1, c-Jun/AP-1, ATF-2, C/EBPa, MyoD, Sp-1 or NF-kB/p65 and various concentrations of T-5224 were added in the multi-well plates precoated with respective consensus double-stranded (ds)DNA oligomers. After incubation for 1 h, the transcription factor bound to its respective consensus dsDNA sequences was detected by using antibodies reactive against the respective transcription factors according to the manufacturer's protocol [1]. |
| 动物实验 | Mice were housed in an SPF (specific pathogen-free) grade environment and provided food and water ad libitum with a 12 h:12 h light/dark cycle. Male 8-week-old DBA/1J mice were immunized with bovine type II collagen emulsified in Freund's complete adjuvant on days 0 and 21. T-5224, MTX and LEF were orally administered once per day. Arthritis was assessed in a blind fashion for four paws per mouse using the following score: 0, uninvolved; 1, swelling of ≤2 toes or slight swelling in ankles and wrists; 2, swelling of ≥3 toes or moderate swelling in ankles and wrists; 3, extensive swelling of total paw. X-ray films of four paws taken using Softex were assessed for joint destruction in 2nd to 5th proximal interphalangeal joints and five metatarsophalangeal joints of four paws, the carpal joints of the forepaws, and the tarsal and calcaneal joints of the hind paws. Score was: 0, no change; 1, partial erosion; 2, complete erosion for joints; and 0, negative; 0.5, positive for osteoporosis. IL-1β (500 ng per unilateral hind paw) was administered into the footpads. The mice with ≥1 arthritis score were treated with either anti-TNFα antibody at 50 or 250 μg/mouse, intraperitoneally (i.p.) twice a week and/or with 3 mg/kg T-5224, orally once daily [1]. |
| 体外活性 | 方法：人表皮角质形成细胞 NHEKs 加入 0.1-1 μM 浓度的 T-5224 ，处理 24 小时后，MTT 法检测细胞活力。
结果：该浓度范围内 T-5224 无细胞毒性、不影响细胞增殖。[1]
方法：HSC-3-M3， OSC-19 中加入梯度浓度 T-5224 （0， 20， 40， 80 μM），划痕后 24 小时测量细胞迁移面积。
结果：T-5224 呈剂量依赖性抑制两种细胞的迁移，80 μM 时迁移几乎被完全抑制。[2] |
| 体内活性 | 方法：8~10 周雌性 BALB/c 小鼠构建 DNFB 模型，模型构建成功后，给药 1% T-5224/1% baricitinib/1% T-5224+1% baricitinib 软膏，每侧耳 25mg，1 次 / 天，共 8 天。
结果：T-5224 显著抑制炎症、恢复 Flg 表达，T-5224 可恢复 Elovl6；T-5224抑制 Il17a/Il17f 。[1]
方法：BALB/c 裸鼠，将 HSC-3-M3 细胞(1×10⁵)注射入舌部，建立原位移植瘤模型，从肿瘤接种后第 1 天开始口服灌胃 T-5224 (150 mg/kg/天)，每日一次，连续给药 4 周。
结果：两组间原发肿瘤体积无显著差异，T-5224 对体重也无明显影响。 颈淋巴结转移率，对照组为 74.1% (20/27)，T-5224 治疗组为 40.0% (12/30)，差异显著。[2] |
| 存储条件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (9.66 mM), Suspension.
H2O : Insoluble
DMSO : 240 mg/mL (463.74 mM), Sonication is recommended.
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| 关键字 | T-5224 | T5224 | T 5224 | MMP | Matrix metalloproteinases | Inhibitor | inhibit | c-Fos/AP-1 | AP-1 | Activator Protein 1 |
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