| 名称 | T-26c |
| 描述 | T-26c is highly potent and selective matrix metalloproteinase-13 (MMP-13) inhibitor (IC50: 6.75 pM). |
| 细胞实验 | Bovine nasal septum cartilage was sliced, and the slices were maintained in the medium of a 1:1 (v/v) mixture of Dulbecco's modified Eagle's MEM and Ham's F-12 medium (DMEM/F-12) containing 10 % fetal calf serum overnight. After confirming that the slices were not contaminated, they were cultured in DMEM/F-12 medium containing 20 μg/mL gentamycin, 50 μg/mL streptomycin, and 50 U/mL penicillin (culture medium) for 2 days at 37 °C. The cartilage slices were cut into small cubes (ca. 1mm3) and transferred individually into wells of a 96 well plate with 100 μL of culture medium. For the collagen degradation assay, the medium was supplemented with 10 ng/mL IL-1β and 50 ng/mL oncostatin M in the presence or absence of compounds. The cartilage was incubated for 2 weeks. The supernatants were harvested and replaced with fresh medium containing identical test compounds every 7 days. Supernatants of day 7 and day 14 were collected and stored at -20 °C until assay. At the end of the culture, the remaining cartilage was completely digested with papain. Hydroxyproline release in the media from each explant was determined as a measure of collagen degradation by use of chloramine T and p-dimethylaminobenzaldehyde. The percentage of inhibitory activity against collagen degradation was calculated as follows: % of inhibition = [(% of collagen degradation with IL-1b and OSM) - (% of collagen degradation with IL-1β, OSM, and test sample)]/[(% of collagen degradation with IL-1β and OSM) - (% of collagen degradation without additives)] × 100. |
| 激酶实验 | The MMP assay buffer consisted of 50 mM Tris–HCl (pH 7.5), 10 mM CaCl2, 150 mM NaCl, and 0.05% Brij-35. The pro-MMPs were activated by preincubation with 1 mM aminophenylmercuric acetate (APMA) in assay buffer at 37 °C for 2 h (MMP-1, 2, 7, 8, 10, and 13) or 18 h (MMP-3 and 9). The TACE assay buffer consisted of 25 mM Tris–HCl (pH 9.0), 2.5 mM ZnCl2, and 0.005% Brij-35. The pro-MMPs were activated by preincubation with 1 mM aminophenylmercuric acetate (APMA) in assay buffer at 37 °C for 2 h (MMP-1, 2, 7, 8, 10, and 13) or 18 h (MMP-3 and 9). Enzyme inhibition assays were performed in an assay buffer containing enzymes and fluorescence peptide (Cy3-PLGLK(Cy5Q)AR-NH2 for MMPs, Cy3-PLAQAV(Cy5QL-2,3-diaminopropionic acid)-RSSSR-NH2 for TACE) in the presence of the various concentrations of inhibitors. Following incubation at 37 °C for 40 min, the reaction was terminated by addition of EDTA (pH 8.0). The increase in fluorescence as measured by Farcyte spectrofluorimeter. Enzyme activity (%) was determined as following equation: Enzyme activity (%) = (X - C)/(T - C) × 100, where X = the fluorescence count with inhibitor, T = the fluorescence count without inhibitor and C = the fluorescence count with EDTA. IC50 values of inhibitors were obtained with iterative fitting package. |
| 体外活性 | T-26c是一种高效且选择性的MMP13抑制剂，IC50值为6.9 pM，对其他相关金属酶的选择性超过2600倍。此外，该抑制剂在牛鼻软骨切片实验中显示出活性。在IL-1b和oncostatin M刺激的软骨中，T-26c显著抑制了胶原蛋白的降解(0.1 μM时的抑制率达87.4%)。 |
| 体内活性 | 通过口服给豚鼠T-26c的二钠盐配方，相较于T-26c自由酸形式（AUC = 6478 ng·h/mL，Cmax = 911 ng/mL），显著提高了AUC（8357 ng·h/mL）和Cmax（1445 ng/mL）。该化合物在所有物种中以10–20 mg/kg的口服剂量被良好吸收。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 12 mg/mL (25.03 mM), Sonication is recommended.
H2O : Insoluble
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1 mg/mL (2.09 mM), Sonication is recommended.
|
| 关键字 | T-26c | T26c | T 26c | MMP-13 | MMP | Matrix metalloproteinases | Inhibitor | inhibit |
| 相关产品 | Doxycycline (hyclate) | Astragaloside IV | Tranexamic acid | Anethole | Meloxicam | Doxycycline | Glucosamine | Methylchloroisothiazolinone/Methylisothiazolinone Mixture | Stigmasterol | Chondroitin sulfate | Propoxur | Edaravone |
| 相关库 | 抑制剂库 | 血管生成库 | 经典已知活性库 | 抗癌化合物库 | 已知活性化合物库 | 抗胰腺癌化合物库 | 抗纤维化化合物库 | 高选择性抑制剂库 | 蛋白酶抑制剂库 | NO PAINS 化合物库 | 膜蛋白靶向化合物库 |
