| 名稱 | Gilteritinib |
| 描述 | Gilteritinib (ASP2215) is a FLT3 inhibitor (IC50=0.29 nM) and an AXL inhibitor (IC50=0.73 nM) with ATP-competitive, selective, and oral activity. Gilteritinib exhibits antitumor activity and can be used to treat FLT3 mutation-positive AML. |
| 細(xì)胞實驗 | Gilteritinib is dissolved in DMSO and stored, and then diluted with appropriate media before use.The effect of Gilteritinib on MV4-11 and MOLM-13 cells is assessed using the CellTiter-Glo Luminescent Cell Viability Assay. Subsequent studies are conducted to examine the effect of Gilteritinib and Quizartinib on Ba/F3 cells expressing either FLT3-ITD, FLT3-D835Y, FLT3-ITD-D835Y, FLT3-ITD-F691 L, or FLT3-ITD-F691I. MV4-11 and MOLM-13 cells are treated with DMSO or increasing concentrations of Gilteritinib (0.01, 0.1, 1, 10, and 100 nM) for 5 days, and cell viability is measured using CellTiter-Glo |
| 激酶實驗 | The kinase inhibitory activity of Gilteritinib is tested against a panel of 78 tested kinases using ATP concentrations that are approximately equal to the Km value for each kinase in a TK-ELISA or off-chip mobility shift assay. Initially, two concentrations of Gilteritinib (1 nM and 5 nM) are tested to assess each compound's inhibitory effect on TK activity. Further studies are then conducted using a dose range of Gilteritinib to determine IC50 values for kinases in which activity is inhibited by >50% with 1 nM Gilteritinib as well as for c-KIT. TK-ELISA and MSA assays are used to conduct IC50 studies for FLT3, LTK, AXL, and c-KIT; the HTRF KinEASE-TK assay is performed to assess the IC50 value of echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) |
| 動物實驗 | MiceAntitumor activity is evaluated in nude mice transplanted with MV4-11 AML cells. The pharmacokinetics in xenografted mice is also investigated. MV4-11 xenografted-mice are treated with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg |
| 體外活性 | 方法：人急性髓細(xì)胞白血病細(xì)胞 MV4-11 和 MOLM-13 用 Gilteritinib (0.01-100 nM) 處理 5 天，使用 CellTiter-Glo 檢測細(xì)胞增殖。
結(jié)果：Gilteritinib 抑制 MV4-11 和 MOLM-13 細(xì)胞的生長，平均 IC50 值分別為 0.92 nM 和 2.9 nM。[1]
方法：人急性髓細(xì)胞白血病細(xì)胞 Molm14 用 Gilteritinib (5-20 nM) 處理 1-24 h，使用 Western Blot 檢測靶點蛋白表達水平。
結(jié)果：當(dāng)與 Molm14 細(xì)胞孵育 1 h 時，Gilteritinib 有效地抑制了 FLT3 及其下游信號通路的活性。但是到 24? h，盡管 FLT3 持續(xù)受到抑制，但 ERK 信號傳導(dǎo)反彈，如 pERK 上調(diào)。[2] |
| 體內(nèi)活性 | 方法：為測試體內(nèi)抗腫瘤活性，將 Gilteritinib (1-10 mg/kg) 口服給藥給攜帶人急性髓細(xì)胞白血病腫瘤 MV4-11 的 Nude 小鼠，每天一次，持續(xù)二十八天。
結(jié)果：在 1 mg/kg/天 (63%)和 3 mg/kg/天 (80%) 劑量下觀察到 MV4-11 腫瘤的顯著生長抑制。并且在 6 mg/kg/天 (93%) 和 10 mg/kg/天 (100%) 劑量下觀察到腫瘤幾乎完全消退。[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 | DMSO : 1 mg/mL
Ethanol : 4 mg/mL (7.2 mM)
H2O : Insoluble
10% DMSO+90% Saline : 0.2 mg/mL (0.36 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 | FLT3 | TAM Receptor | CD135 | Axl | inhibit | Gilteritinib | Mer | ASP-2215 | Tyro3 | Fms like tyrosine kinase 3 | Cluster of differentiation antigen 135 | ASP 2215 | Inhibitor |
| 相關(guān)產(chǎn)品 | Imatinib | Axitinib | Sorafenib tosylate | Lenvatinib mesylate | Regorafenib | Pazopanib | Nintedanib | Dasatinib | Sorafenib | Pexidartinib | Regorafenib monohydrate | Fedratinib |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 激酶抑制劑庫 | FDA 上市藥物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 抗癌藥物庫 |