| 名稱 | Ketoconazole |
| 描述 | Ketoconazole (R-41400), a CYP3A4 inhibitor, is an imidazole anti-fungal agent. |
| 細(xì)胞實(shí)驗(yàn) | HT29-S-B6 cells (5×105) are plated in 35-mm Petri dishes. The next day, the medium is changed and effectors are added in a small volume (10-20 μL). The incubation medium is renewed every day during the experiments. The same triplicate dishes are used for cell counts, [3H]thymidine incorporation, and flow cytometry. [3H]Thymidine (0.5 μCi) is allowed to incorporate for 24 hours; at the end of incubation, cells are rinsed with 1 mL of medium, detached with 1 mL of trypsin-EDTA, and diluted (1:3) with the culture medium. An aliquot (0.5-1 mL) is used for cell count with a Coulter Counter.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Whole Cell [3H]R1881 Binding Assay: Fibroblasts are grown to confluence in five or six 150 cm2 tissue culture flasks for routine assay. This usually requires 4-6 weeks from the time of the initial seeding of the cell line. All studies are performed between passages 3-20. Two days before assay, the medium is changed to one lacking fetal calf serum. This is repeated again 24 hours before assay. Competition assays are performed with 0.5-1.0 nM [3H]R1881 and increasing amounts of the nonradioactive compounds. Binding to low affinity sites is determined in the presence of 5 × 10-7 M R1881 and is subtracted from whole cell binding of [3H]R 1881 obtained in the absence of any inhibitor to assess binding to 5 high affinity site |
| 體外活性 | 腹腔注射Ketoconazole（25 mg/kg）后,大鼠體內(nèi)血漿皮質(zhì)酮濃度明顯降低,也可使低劑量可卡因自我給藥減少.Ketoconazole處理組大鼠,地高辛生物有效性得到提高,從0.68提高至0.84 ,而平均吸收時(shí)間從1.1 h減少至0.3 h.此外,地高辛的口服AUC值也得到提高,從63 mg·h/L提高至411 mg·h/L.地高辛的靜脈注射AUC值也被提高,從93 mg·h/L提高至486 mg·h/L. |
| 體內(nèi)活性 | 在HT29-S-B6結(jié)腸癌細(xì)胞中,Ketoconazole劑量依賴性地降低細(xì)胞增殖,[3H]胸苷滲透,IC50為2.5 mM。在Evsa-T細(xì)胞系和MDA-MB-231 細(xì)胞系中,Ketoconazole抑制[3H]胸苷滲透,IC50 分別為2 μM 和13 μM。在HT29-S-B6細(xì)胞中,Ketoconazole在24 h內(nèi),劑量依賴性地誘導(dǎo)S期細(xì)胞數(shù)減少（從17%降低至3%）,Go-G1期細(xì)胞百分?jǐn)?shù)則相應(yīng)增加（從64% 增加至80%）。通過(guò)與[3H]Dexamethasone競(jìng)爭(zhēng)性結(jié)合的方式,Ketoconazole能夠抑制成纖維細(xì)胞糖皮質(zhì)激素受體,IC50為0.3 mM。幾種馬拉色霉菌種對(duì)Ketoconazole較為敏感,最小抑制濃度為0.03 μg/mL。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 5.31 mg/mL (10 mM), Sonication is recommended.
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| 關(guān)鍵字 | Inhibitor | Ketoconazole | inhibit | Fungal | Cytochrome P450 | R 41400 | Ras | Ketoconazol | CYPs | R41400 |
| 相關(guān)產(chǎn)品 | Naringin | 2-Butyl-1,2-benzisothiazolin-3-one | Potassium gluconate | Dehydroacetic acid sodium | Geraniol | Paclobutrazol | Veratraldehyde | Lauryl betaine | Methyl 2-amino-5-bromobenzoate | Chlorobutanol hemihydrate | Naringenin | Chitosan (MW 150000) |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 抗真菌庫(kù) | 激酶抑制劑庫(kù) | 抗衰老化合物庫(kù) | GPCR靶點(diǎn)分子庫(kù) | 膜蛋白靶向化合物庫(kù) | FDA 上市激酶抑制劑庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |