T-5224

中文名称：T-5224
CAS号：530141-72-1
中文别名：3-(5-(4-(环戊基氧基)-2-羟基苯甲酰基)-2-((3-羟基-1,2-苯并异恶唑-6-基)甲氧基)苯基)丙酸;化合物T-5224;T-5224试剂;T-5224,S8966;T-5224抑制剂;T-5224试剂;T-5224抑制剂
英文名称：T-5224
英文别名：Benzenepropanoicacid,5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(2,3-dihydro-3-oxo-1,2-benzisoxazol-6-yl)Methoxy]-;T-5224;3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-oxo-2,3-dihydrobenzo[d]isoxazol-6-yl)methoxy);3-(5-(4-Chemicalbook(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo-[d]isoxazol-6-yl)methoxy)phenyl);T-5225;3-[5-[4-(cyclopentoxy)-2-hydroxy-benzoyl]-2-[(3-hydroxy-1,2-benzoxazol-6-yl)methoxy]phenyl]propanoicacid;CS-1217;T-5224;T5224;T5224.
分子式：C29H27NO8
分子量：517.53

溶解性：溶于水，易溶于DMSO。

简介：

T-5224 是选择性的转录因子c-Fos/activator protein (AP)-1抑制剂，具有抗炎作用，能够特异性抑制 c-Fos/c-Jun 的 DNA 结合活性，但对其他转录因子的结合活性无影响。它抑制 IL-1β 诱导的 Mmp-3、Mmp-13、Adamts-5 转录上调。

靶点活性：

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，MMP1 (SW982 cells):10 μM, β-hexosaminidase (RBL-2H3 cells):18.30 ± 1.48 µM, AP-1 (NIH3T3 cells):10 μM。

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 。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 。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。

体内活性：

腹膜内注射 LPS 后给予 T-5224（300 mg/kg，口服）可显著防止血清 TNFα、HMGB1、ALT/AST 水平以及肝组织 MIP-1α 和 MCP-1 水平的急性升高，并降低致死率（27%）。在大鼠和猴肝微粒体中观察到 G2 是 T-5224 的主要代谢物，这表明 G2 不是人类特异性代谢物。T-5224（300 mg/kg，口服）可抑制 C57BL/6 小鼠中 TNF-alpha 和其他下游效应物的产生。

应用示例：

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

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 .

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 .

注意事项：

本产品仅限科研用途。