| 名稱 | G-749 |
| 描述 | G-749, a new-type FLT3 inhibitor, exhibits effective and sustained inhibition of the FLT3 wild type and mutants. |
| 細胞實驗 | Cells are seeded at a density of 2 ×104 cells per well and treated with the indicated concentrations of test inhibitor for 72 hours at 37℃. The conditioned medium (CM) is prepared from HS-5 cell culture for 5 days under routine culture conditions, clarified by centrifugation, and used immediately. The CM is added to complete medium at a final concentration of 35%. In coculture experiments, 5 ×104 AML blast cells are plated in 24-well plates containing 1 ×104 HS-5 monolayers and then cultured for at least 48 hours before the exposure of inhibitors. Cell viability is determined by an ATPLite assay. (Only for Reference) |
| 激酶實驗 | Kinase assay: Activity assays are conducted using Lance Ultra time-resolved fluorescence resonance energy transfer (TR-FRET) technology from Perkin-Elmer. Briefly, 10 ng/mL FLT3 enzyme, a serial diluted G-749, 80 nM substrate of ULight-poly-GT peptide and variable amounts of ATP (8.5 μM to 1088 μM) are mixed in kinase assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT and 0.01% Tween-20) and are added to a 384-well OptiPlate-384 in a volume of 10 μL. Kinase reactions are incubated at room temperature for up to 1 h and then stopped by the addition of 5 μL of 10 mM EDTA. A volume of 5 μL of the specific Eu-labeled-anti-phosphopeptide antibody diluted in LANCE Detection Buffer is then added to a final concentration of 2 nM. After 30-minute incubation, assay plates are incubated at 23°C and the LANCE signal is measured on an EnVision Multilabel Reader. Excitation wavelength is set at 320 nm and emission monitored at 615 nm (donor) and 665 nm (acceptor). The IC50 is calculated using nonlinear regression analysis analysis by GradPad Prism 5. |
| 體外活性 | 在Molm-14細胞骨髓移植模型中,口服 G-749（20 mg/kg）,能夠抑制腫瘤生長.在MV4-11異種移植的小鼠模型中,口服 G-749（30 mg/kg）通過抑制FLT3通路,并顯著抑制腫瘤細胞生長. |
| 體內活性 | 在AML患者的原始細胞中,G-749通過誘導細胞凋亡,能夠抑制細胞增殖。在穩(wěn)定表達FLT3-ITD/N676D,FLT3-ITD/F691L,FLT3-D835Y,或FLT3-D835Y/N676D的BaF3細胞系中（IC50 <10 nM）,G-749具有顯著的抑制活性。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 11.36 mg/mL (21.79 mM), Sonication is recommended.
10% DMSO+90% Saline : 1.14 mg/mL (2.19 mM), Suspension.
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| 關鍵字 | tyrosine | TAMReceptor | TAM Receptor | RET | resistance | receptor | myeloid | Mer | leukemia | kinase | Inhibitor | inhibit | G-749 | G 749 | Fms-like | Fms like tyrosine kinase 3 | FLT3 (D835Y) | FLT3 | drug | cRET | Cluster of differentiation antigen 135 | CD135 | AuroraKinase | Aurora Kinase | Aurora B | Apoptosis | AML | acute |
| 相關產品 | Urea | Formamide | Dimethyl phthalate | Aceglutamide | Alginic acid | Dextran sulfate sodium salt (MW 5000) | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen | Adenosine |
| 相關庫 | 抑制劑庫 | 血管生成庫 | 經典已知活性庫 | 已知活性化合物庫 | 細胞周期化合物庫 | ReFRAME 相關化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 血液病分子庫 | 抗肺癌化合物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 |