| 名称 | T-5224 |
| 描述 | T-5224 is a transcription factor c-Fos/AP-1 inhibitor, which specifically inhibits the DNA binding activity of c-Fos/c-Jun without affecting other transcription factors. |
| 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 | IL-1b刺激下的人类滑膜SW982细胞产生滑膜细胞介质MMP-1、MMP-3、IL-6和TNFα的体外生产，以及IL-1b刺激下的人类软骨细胞SW1353细胞产生软骨炎症介质MMP-3和MMP-13，均被T-5224所抑制。大多数细胞实验的IC50值约为10μM [1]。加压素选择性地刺激CDS1 mRNA的增加，这一过程依赖于蛋白激酶C，并可被AP-1抑制剂T-5224所抑制 [3]。T-5224显著以剂量依赖的方式抑制HNSCC细胞的侵袭、迁移和MMP活性；而对细胞增殖没有显著影响 [4]。 |
| 体内活性 | T-5224通过每日一次从第21天开始使用，有效抑制了胶原蛋白诱导的关节炎(CIA)的发展，在第50天时，3 mg/kg和30 mg/kg剂量的T-5224分别抑制了关节炎的发展64%和91%。接受T-5224治疗的小鼠体重稳定恢复。X光研究显示，接受治疗的关节破坏得到了抑制，未经治疗的关节炎对照组则没有这种现象，特别是，30 mg/kg的T-5224完全保护了关节不受破坏[1]。在腹腔注射LPS后，口服给予T-5224 (300 mg/kg)能显著保护，对抗急性血清TNFα、HMGB1、ALT/AST水平的升高以及肝组织中MIP-1α和MCP-1的水平，减少了致死率(27%)[2]。T-5224 (150 mg/kg)或安慰剂每日口服4周。在模型中，接受T-5224治疗组的颈淋巴结转移率为40.0%，而安慰剂治疗组为74.1%[4]。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (9.66 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
H2O : Insoluble
DMSO : 16.67 mg/mL (32.2 mM)
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| 关键字 | Activator Protein 1 | Inhibitor | inhibit | T-5224 | Matrix metalloproteinases | MMP | T 5224 | AP-1 | T5224 |
| 相关产品 | Doxycycline (hyclate) | Astragaloside IV | Bovine Type II Collagen | Arctigenin | Fenofibric acid | Triolein | Doxycycline | Glucosamine | Stigmasterol | Glucosamine sulfate | Ethyl gallate | Edaravone |
| 相关库 | 抑制剂库 | 血管生成库 | 经典已知活性库 | 已知活性化合物库 | 转录因子库 | ReFRAME 相关化合物库 | 抗衰老化合物库 | 蛋白酶抑制剂库 | 抗COVID-19化合物库 | NO PAINS 化合物库 |
