JI6 是一种有效，选择性和具有口服活性的FLT3抑制剂，抑制FLT3-WT，FLT3-D835Y和FLT3-D835H的IC50值分别为 ~40，8 和 4 nM。JI6 还抑制JAK3和c-Kit，IC50值分别为 ~250 和 ~500 nM。JI6 可用于急性髓性白血病的研究。
| 生物活性 | JI6 is a potent, selective and orally activeFLT3inhibitor, withIC50s of ~40, 8, and 4 nM forFLT3-WT,FLT3-D835Y, andFLT3-D835H, respectively. JI6 also inhibitsJAK3andc-Kit, withIC50s of ~250 and ~500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia[1]. |
| IC50& Target[1] | FLT3-D835H 4 nM (IC50) | FLT3-D835Y 8 nM (IC50) | FLT3-WT 40 nM (IC50) | JAK3 ~250 nM (IC50) | c-Kit ~500 nM (IC50) |
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体外研究
(In Vitro) | JI6 (3-1000 nM; 1-4 days) 以剂量依赖性方式抑制 MV4-11 细胞的活力，IC50值为 ~25 nM[1]。
JI6 (1-2000 nM; 48 h) 有效抑制表达 FLT3-ITD，FLT3-D835Y 和 FLT3-D835H 的 HCD-57 细胞的活力，IC50值为 ~40 nM，对亲代 HCD-57 或表达 JAK2V617F 的细胞基本没有影响[1]。
JI6 (100-500 nM; 24 h) 在表达 FLT3-ITD 和 FLT3-D835Y 的 HCD-57 细胞中诱导细胞凋亡和细胞周期停滞[1]。
JI6 (50-500 nM; 3 h) 抑制表达 FLT3-ITD 和 FLT3-D835Y 的 HCD-57 细胞中 FLT3 及 ERK 和 Akt 的磷酸化[1]。
Cell Viability Assay[1] | Cell Line: | MV4-11, HL60, Karpas 299, and Jurkat cells | | Concentration: | 3-1000 nM | | Incubation Time: | 48 hours | | Result: | Inhibited MV4-11 cells and no effects of JI6 on the three remaining cells at a concentration as high as 1 μM. |
Apoptosis Analysis[1] | Cell Line: | FLT3-ITD- and FLT3-D835Y-transformed HCD-57 cells | | Concentration: | 100, 500 nM | | Incubation Time: | 24 hours | | Result: | Increased the percentage of apoptotic and necrotic cells and displayed no effects on the apoptosis of the parent HCD-57 cells. |
Cell Cycle Analysis[1] | Cell Line: | FLT3-ITD- and FLT3-D835Y-transformed HCD-57 cells | | Concentration: | 100, 500 nM | | Incubation Time: | 24 hours | | Result: | Significantly reduced G2 and S phase cells and increased G1 phase cells in both FLT3-ITD and D835Y cells. |
Cell Viability Assay[1] | Cell Line: | FLT3-ITD- and FLT3-D835Y-transformed HCD-57 cells | | Concentration: | 50, 100, 500 nM | | Incubation Time: | 3 hours | | Result: | Inhibited phosphorylation of FLT3, ERK1, ERK2 and Akt. |
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体内研究
(In Vivo) | JI6 (15 mg/kg; i.p. daily for 3 weeks) 抑制免疫缺陷小鼠体内表达 FLT3-D835Y 的 HCD-57 增殖并延长小鼠存活期[1]。
JI6 (25 mg/kg; p.o. daily for 3 weeks) 抑制 FLT3-ITD 敲入小鼠的骨髓增生表型[1]。
JI6 (100 mg/kg; a single i.p.) 在表达 FLT3-D835Y 的小鼠中显着抑制 FLT3 磷酸化和下游信号转导[1]。
| Animal Model: | NSG mice (10-12 weeks old, male) were implanted with FLT3-D835Y-transformed HCD-57 cells[1] | | Dosage: | 15 mg/kg | | Administration: | I.p. daily for 3 weeks | | Result: | Reduced the spleen size and prolonged the survival of these mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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