| 名稱 | T-26c |
| 描述 | T-26c is highly potent and selective matrix metalloproteinase-13 (MMP-13) inhibitor (IC50: 6.75 pM). |
| 細(xì)胞實(shí)驗 | 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. |
| 激酶實(shí)驗 | 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. |
| 體外活性 | T-26c是一種高效且選擇性的MMP13抑制劑，IC50值為6.9 pM，對其他相關(guān)金屬酶的選擇性超過2600倍。此外，該抑制劑在牛鼻軟骨切片實(shí)驗中顯示出活性。在IL-1b和oncostatin M刺激的軟骨中，T-26c顯著抑制了膠原蛋白的降解(0.1 μM時的抑制率達(dá)87.4%)。 |
| 體內(nèi)活性 | 通過口服給豚鼠T-26c的二鈉鹽配方，相較于T-26c自由酸形式（AUC = 6478 ng·h/mL，Cmax = 911 ng/mL），顯著提高了AUC（8357 ng·h/mL）和Cmax（1445 ng/mL）。該化合物在所有物種中以10–20 mg/kg的口服劑量被良好吸收。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 12 mg/mL (25.03 mM)
H2O : Insoluble
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| 關(guān)鍵字 | T-26c | T26c | Inhibitor | Matrix metalloproteinases | MMP | T 26c | inhibit |
| 相關(guān)產(chǎn)品 | Doxycycline (hyclate) | Astragaloside IV | Bovine Type II Collagen | Arctigenin | Fenofibric acid | Triolein | Doxycycline | Glucosamine | Stigmasterol | Glucosamine sulfate | Ethyl gallate | Edaravone |
| 相關(guān)庫 | 抑制劑庫 | 血管生成庫 | 經(jīng)典已知活性庫 | 抗癌化合物庫 | 已知活性化合物庫 | 抗胰腺癌化合物庫 | 抗纖維化化合物庫 | 高選擇性抑制劑庫 | 蛋白酶抑制劑庫 | NO PAINS 化合物庫 |