| 名稱 | BI 2536 |
| 描述 | BI2536 is an effective Plk1 inhibitor (IC50: 0.83 nM). It has 4- and 11-fold greater selectivity than Plk2 and Plk3. |
| 細胞實驗 | Cell proliferation assays were performed by incubation in the presence of various concentrations of BI 2536 for 72 hr, and cell growth was assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth was inhibited by 50% (EC50) were extrapolated from the dose-response curve fit [1]. |
| 激酶實驗 | Recombinant human Plk1 (residues 1–603) was expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1, Plk2, and Plk3 were performed in the presence of serially diluted inhibitor with 20 ng of recombinant kinase and 10 μg casein from bovine milk as the substrate. Kinase reactions were performed in a final volume of 60 μl for 45 min at 30C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi g-P33-ATP). Reactions were terminated by the addition of 125 μl of ice-cold 5% TCA. After transfer of the precipitates to MultiScreen mixed ester cellulose filter plates, plates were washed with 1% TCA and quantified radiometrically. Dose-response curves were used for calculating IC50 values [1]. |
| 動物實驗 | Female BomTac:NMRI-Foxn1nu mice were grafted subcutaneously with HCT 116 colon-carcinoma, NCI-H460, or A549 lung carcinoma cells by subcutaneous injection, respectively, of 2 × 10^6, 1 × 10^6, and 1 × 10^7 cells into the flank of each mouse. When tumors reached a volume of approximately 50 mm^3, animals were pair-matched into treatment and control groups of ten mice each. In regression experiments, treatment was not initiated until the mean tumor volume reached 500 mm^3. BI 2536 was formulated in hydrochloric acid (0.1 N), diluted with 0.9% NaCl, and injected intravenously into the tail vein at the indicated dose and schedule. The administration volume was 10 ml per kg body weight. Tumor volumes were determined three times a week with a caliper. The results were converted to tumor volume (mm^3) by the following formula: length × width2 × π/6. The weight of the mice was determined as an indicator of tolerability on the same days. For statistical analysis, the treatment group was compared with the vehicle control group in a one-sided (decreasing) exact Wilcoxon test [1]. |
| 體外活性 | BI 2536以低納摩爾濃度抑制Plk1酶活性。該化合物在具有不同組織起源和癌基因組特征的人類癌癥細胞系中強效引起有絲分裂阻滯并誘導凋亡[1]。使用納摩爾劑量的BI 2536處理后，ATC細胞正常通過S期，但之后因有絲分裂阻滯直接死亡。與ATC細胞相比，非轉化的甲狀腺細胞對BI 2536誘導的細胞周期效應的敏感性降低了3.2至18.4倍[2]。 |
| 體內活性 | BI 2536 在裸鼠人類腫瘤異種移植物中抑制生長，并通過耐受性良好的靜脈注射劑量方案誘導大型腫瘤退化。在處理過的腫瘤中，細胞在前期停滯，磷酸化組蛋白H3積累，并且包含異常的有絲分裂紡錘體[1]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 93 mg/mL (178.3 mM)
DMSO : 13.33 mg/mL (25.56 mM), Sonication is recommended.
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| 關鍵字 | BI-2536 | Apoptosis | Epigenetic Reader Domain | Inhibitor | BI 2536 | BI2536 | inhibit | Polo-like Kinase (PLK) |
| 相關產品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Curcumin | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
| 相關庫 | 抑制劑庫 | 經典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 高選擇性抑制劑庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |