| 名稱 | Imatinib |
| 描述 | Imatinib (STI571) is a multi-targeted receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of BCR/ABL, v-Abl, PDGFR, and c-kit with oral activity. Imatinib has antitumor activity for the treatment of chronic granulocytic leukemia. |
| 細胞實驗 | M-07e cells were grown in serum-free RPMI 1640 at 37°C for approximately 18 hours before they were incubated for 90 minutes in the presence of various concentrations of STI 571. The cells were then pelleted and resuspended in 1 mL RPMI 1640. STI 571 was added to each tube to achieve the same concentration used during the 90 minutes of preincubation. The cells were then incubated with inhibitor and growth factor (SLF or GM-CSF) for 15 minutes at 37°C. Subsequently, the cell pellets were lysed with 100 to 250 μL of protein lysis buffer (50 mmol/L Tris, 150 mmol/L sodium chloride, 1% NP-40, and 0.25% deoxycholate, with addition of the inhibitors aprotinin, leupeptin, pepstatin, phenylmethyl sulfonyl fluoride, and sodium orthovanadate). Western immunoblot analysis was performed as previously described.41Experiments with HMC-1 cells were performed in the same way except that neither SLF nor GM-CSF was added [1]. |
| 動物實驗 | Swiss mice (nu/nu, female), weighing 30 g, 6 – 8 weeks old, were bred in the animal facilities, maintained under specific pathogen-free conditions with artificial lighting (12 hr light/12 hr dark cycle) and fed a regular diet and water ad libitum. For therapeutic trials, the tumor-bearing mice were randomly divided into equivalent groups of 5 to 12 animals and mice were treated as soon as the xenografted tumors reached a diameter of 5 mm (or a tumor volume of approximately 60 mm^3). Four different human tumors were used: the SCLC6, SCLC61, SCLC 74 and SCLC108 small cell lung cancers. STI571 was administered at a total dosage of 70 or 100 mg/kg per day in 1 or 2 intraperitoneal injections, with or without etoposide plus ifosfamide or topotecan. STI571 was diluted in 150 l of H2O and administered on different days, as indicated. Etoposide and ifosfamide were diluted in 200 l of 0.9% sodium chloride, and topotecan was diluted in 150 l of 0.9% sodium chloride. The control group received injections according to the same schedule as experimentally treated mice. All mice were weighed once weekly. Tumor growth was monitored by measuring 2 perpendicular diameters with calipers. Tumor volume (V) and the relative tumor volume (RTV) were calculated as:. V = a^2 × b/2,. where a is the width (large diameter) and b the length (small. diameter) of the tumor in millimeters, and. RTV = Vx/Vi,. where Vx is the mean tumor volume in cubic millimeters at any given time and Vi is the mean initial tumor volume in cubic millimeters at the start of treatment. Mice were ethically sacrificed when the tumor volume reached 2,500 mm^3 [5]. |
| 體外活性 | 方法：人、小鼠和大鼠的骨肉瘤細胞用 Imatinib (1-40 μM) 處理 72 h，使用 XTT assay 檢測細胞活力。
結(jié)果：Imatinib 以劑量依賴性方式降低了活骨肉瘤細胞的數(shù)量，72 h 的 IC50 為：20 μM (MG-63)、11 μM (HOS)、23 μM (MOS-J)、15 μM (POS-1)、9 μM (OSRGA）。[1]
方法：人胃癌細胞 AGS、MKN45 和 SNU638 用 Imatinib (30-100 μM) 處理 48 h，使用 Flow Cytometry 檢測細胞凋亡情況。
結(jié)果：Annexin V/PI-positive 細胞的百分比顯著增加，表明 Imatinib 治療增加了腫瘤細胞的早期凋亡。[2] |
| 體內(nèi)活性 | 方法：為研究抗腫瘤活性，將 Imatinib (25-100 mg/kg) 口服給藥給攜帶未分化 POS-1 或混合成骨細胞/溶骨 MOS-J 骨肉瘤腫瘤的小鼠，每天一次，持續(xù) 21 或 43 天。
結(jié)果：Imatinib 在體內(nèi)抑制骨肉瘤的進展。[1]
方法：為研究對多發(fā)性硬化癥 (MS) 的作用，將 Imatinib (60 mg/kg) 口服給藥給 EAE C57BL/6 小鼠模型，每周六次，持續(xù)兩周。
結(jié)果：Imatinib 通過減輕疾病的嚴重程度和延遲發(fā)病，對 EAE 有有益的影響。Imatinib 及其潛在的治療作用和免疫調(diào)節(jié)特性可被考慮用于治療多發(fā)性硬化癥。[3] |
| 存儲條件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2.50 mg/mL (5.06 mM), Solution.
DMSO : 25.00 mg/mL (50.65 mM), Sonication is recommended.
|
| 關(guān)鍵字 | v-Abl | STI-571 | STI 571 | ST1571 | ST 1571 | SCFR | SARS-CoV | SARSCoV | SARS coronavirus | Platelet-derived growth factor receptor | PDGFR | Inhibitor | inhibit | Imatinib | c-Kit | cKit | CGP-57148B | CD117 | Bcr-Abl | BcrAbl | Autophagy |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Aceglutamide | Alginic acid | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Adenosine | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抗癌上市藥物庫 | 經(jīng)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 | 臨床失敗化合物庫 | EMA 上市藥物庫 | 抗衰老化合物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | FDA 上市激酶抑制劑庫 | 藥物功能重定位化合物庫 |