| 名稱 | Tacrolimus |
| 描述 | Tacrolimus (Fujimycin) is a macrolide antibiotic that binds to FKBP12 to form a high-affinity complex (Ki=0.2 nM) that inhibits calcium/calmodulin-dependent protein phosphatase activity. Tacrolimus is an immunosuppressant that inhibits the overall suppression of T-lymphocytes by inhibiting the release of IL-2. |
| 細(xì)胞實驗 | Tumor cell proliferation was determined by the MTT. Briefly, after MH3924A cells had reached the logarithmic growth phase, a 0.2-ml cell suspension at 1×10^4 cells/ml was added into each well of a 96-well plate and cultured in DMEM with 10% FBS, 10 μg/l vascular endothelial growth factor and 0.1 g/l heparin for 24 h. When adherent growth was established, different concentrations of FK506 (10, 100 and 1,000 μg/l), AMD3100 (10, 50 and 100 μg/l) and FK506 (0 and 100 μg/l) + AMD3100 (0, 10, 50 and 100 μg/l) were added into the plates. Untreated cells cultured in medium alone were used as controls. After culturing for 48 h, 10 μl MTT (5 g/l) was added, and each well was incubated for 6 h; next, 150 μl/well dimethyl sulfoxide was added, followed by measurements of the absorbance at 570 mm on a spectrophotometer reader. Each well was measured three times, and each sample was assayed in triplicate [2]. |
| 動物實驗 | Experiments were performed in 16 healthy August Copenhagen Irish rats (male, 16–20 weeks, weighing 240–300 g). The rat model of liver tumor was established as follows: First, MH3924A cells were collected and injected into the alar skin of rats. The tumors were removed from alar skin when grown to 2×1×1 mm3, and intrahepatic tumor implantation of rats was performed under aseptic conditions as described previously (25,26). Five days later, rats were randomly divided into two groups: one group was subcutaneously injected with normal saline for 14 days (NS group, n=8, 3 mg/kg/day), and the second group was subcutaneously injected with FK506 for 14 days (FK506 group, n=8, 0.3 mg/kg/day). Forty days following implantation, rats were sacrificed, and the weight of tumor, the volume of the fluid in the ascites, the incidence of lymphatic metastasis in the abdominal cavity and of abdominal wall metastasis were measured. In addition, the lungs were irrigated with 15% Indian ink, followed by counting of the number of metastatic nodules in the lung. The tumor and adjacent tissues, as well as healthy liver tissues, were harvested and preserved in 4% formalin for later use [2]. |
| 體外活性 | 方法：大鼠肝癌細(xì)胞 MH3924A 用 Tacrolimus (10-1000 μg/L) 處理 48 h，使用 MTT assay 檢測細(xì)胞活力。
結(jié)果：用低濃度 Tacrolimus (10 μg/L) 處理對 MH3924A 細(xì)胞的增殖沒有顯著影響。在用更高濃度的 Tacrolimus (100-1000 μg/L) 處理后，MH3924A 細(xì)胞的增殖顯著增強(qiáng)。[1]
方法：人腎上皮細(xì)胞 HK-2 用 Tacrolimus (1-20 μM) 處理 48 h，使用 resazurin reduction assay 測定細(xì)胞活力。
結(jié)果：12 μM Tacrolimus 不會導(dǎo)致 resazurin 轉(zhuǎn)化率的顯著變化，而 14-20 μM Tacrolimus 導(dǎo)致 resazulin-reduction 的統(tǒng)計學(xué)顯著降低，表明 Tacrolimus 處理后 HK-2 細(xì)胞的活力降低。[2] |
| 體內(nèi)活性 | 方法：為測試體內(nèi)免疫抑制活性，將 Tacrolimus (4 mg/kg in Cremaphor) 腹腔注射給酒精/四氯化碳誘導(dǎo)的大鼠肝纖維化模型，每天一次，持續(xù)四周。
結(jié)果：Tacrolimus 完全阻止了酒精/四氯化碳誘導(dǎo)的大鼠肝纖維化的發(fā)展。Tacrolimus 處理的肝臟中沒有肝星狀細(xì)胞的激活，膠原 α2（I）mRNA 的表達(dá)處于正常水平。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 80.4 mg/mL (100 mM)
DMSO : 45 mg/mL (55.97 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 8.04 mg/mL (10 mM), 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.
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| 關(guān)鍵字 | FKBP | FK506-binding protein | Inhibitor | Phosphatase | Bacterial | FR-900506 | Antibiotic | FK 506 | FK-506 | inhibit | FR 900506 | Tacrolimus | Autophagy |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Doxycycline | Neomycin sulfate | Hydroxychloroquine | Dimethyl sulfoxide | Stavudine | Ampicillin sodium | Sulfamethoxazole sodium | Paeonol | Kanamycin sulfate |
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