| 名稱 | Radotinib |
| 描述 | Radotinib (IY-5511), and sometimes referred to by its investigational name IY5511, is a drug for the treatment of different types of Y, most notably Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) with resistance or intolerance of other tyrosine kinase Bcr-Abl inhibitors |
| 細胞實驗 | Cells are seeded in 96-well plates at a density of 2×104 cells/ml with 100 μL of medium per well and then incubated with various concentrations of radotinib (0, 1, 10, and 100 μM) for 72 h at 37°C. The CellTiter 96 solution (20 μL) is added directly to each well and plates are incubated for 4 h in a humidified 5% CO2 atmosphere at 37°C. Absorbance is measured with a PowerWave XS2 Microplate Spectrophotometer at 490 nm and the results are expressed as percentage changes from the basal condition using four to five culture wells for each experimental treatment. In some experiments, HL60 cells are cultured with 100 nM ATRA and 1 μM dasatinib for 4 days, and 10 μM radotinib is added to each group according to the planned schedule(Only for Reference) |
| 激酶實驗 | Autophosphorylation of EGFR in cells: For experiments using cells in culture, A431 cells are treated with various concentrations of Pelitinib for 2.75 hours before co-incubation with 100 ng/mL EGF for 0.25 hour. Cells are washed twice with cold phosphate-buffered saline (PBS) before adding to lysis buffer (10 mM Tris, pH 7.5, 5 mM ethylenediamine tetra-acetic acid (EDTA), 150 mM NaCl, 1% Triton X-100, 1% Sodium deoxycholate, 0.1 % SDS, 1 mM PMSF, 10 mg/mL pepstatin A, 10 mg/mL leupeptin, 20 KIU/mL aprotinin, 2 mM sodium orthovanadate, and 100 mM sodium fluoride) for 20 minutes on ice, before immunoprecipitation and SDS-PAGE-immunoblotting. For immunoprecipitation, cultured cells are placed in cold lysis buffer and immediately homogenized on ice with a polytron with several pulses. The homogenate is first centrifuged at 2500 rpm (20 minutes, 4 °C) and then again at 14,000 rpm in a microcentrifuge (10 minutes, 4 °C). Supernatants (1000 μg protein) are incubated for 2 hours at 4 °C with 15 mL of EGFR polyclonal antibody. After 2 hours, 50 μL of protein G plus/protein A agarose beads is added and incubated with constant rotation for 2 hours at 4 °C. After washing with lysis buffer, beads are boiled for 2 minutes in Laemmli sample buffer. Proteins are then resolved by SDS-PAGE, transferred to immobilon membrane and probed overnight with an anti-phosphotyrosine antibody conjugated with horseradish peroxidase (HRP). Membranes are developed using the ECL reagent. Total EGFR protein is determined by stripping membranes and re-probing with receptor-specific antibodies. Quantitation of bands is done by densitometry, using ImageQuant software with a Molecular Dynamics laser transmittance scanner. |
| 體外活性 | 體外實驗中，Radotinib結合BCR-ABL1并減少了其目標蛋白CrkL的磷酸化。Radotinib還有效抑制了BCR-ABL1常見突變克隆的增殖，T315I突變除外。[1] 在AML細胞中，Radotinib顯著降低了細胞活性，促進了分化，并誘導了CD11b表達和凋亡。在NB4、THP-1和Kasumi-1細胞中，Radotinib也誘導CD11b表達，并降低了細胞的活性。[2] |
| 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 : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 5.3 mg/mL (10 mM)
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| 關鍵字 | IY5511 | IY 5511 | Radotinib |
| 相關產(chǎn)品 | Ponatinib | Pivanex | Imatinib | Bosutinib hydrate | KW-2449 | Masitinib | Nilotinib monohydrochloride monohydrate | Bosutinib | GNF-5 | Dasatinib | Imatinib Mesylate | Nilotinib |
| 相關庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 激酶抑制劑庫 | FDA 上市激酶抑制劑庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌藥物庫 |