| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Preparation Method | Two concentrations of gilteritinib(1 nM and 5 nM) were tested to assess the inhibitory effect of each compound on TK activity and then a range of doses of gilteritinib was used for further studies to determine the IC 50 value of the kinase. |
Reaction Conditions | 1 nM and 5 nM Gilteritinib and protein |
Applications | Gilteritinib inhibited the activity of eight of the 78 tested kinases by over 50% at concentrations of either 1 nM (FLT3, LTK, ALK, and AXL) or 5 nM (TRKA, ROS, RET, and MER). The IC50 values were 0.29 nM for FLT3 and 0.73 nM for AXL. Gilteritinib inhibited FLT3 at an IC50 value that was approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM). |
Cell lines | MV4-11 cells |
Preparation Method | MV4-11 cells were treated with DMSO or increasing concentrations of gilteritinib for 5 days, and cell viability was measured using CellTiter-Glo. |
Reaction Conditions | 10-11-10-7M gilteritinib for 5days |
Applications | After 5 days of treatment,gilteritinib inhibited the growth of MV4-11 and MOLM-13 cells with mean IC 50 values of 0.92 nM(95%CI :0.23-3.6 nM) and 2.9 nM(95%CI :1.4-5.8 nM). |
Animal models | Female NOD-SCID mice |
Preparation Method | In the intra-bone marrow transplantation (IBMT) model, MV4 11-luc cells (1 106 cells/mouse) were injected into the bone marrow of the left tibia of female NOD-SCID mice (day 0). After confirming tumor cell engraftment at day 14, mice were orally administered with once-daily vehicle control or gilteritinib at 30 mg/kg from day 15 to day 70. Tumor growth was monitored once a week during the dosing period and then every other week until day 100. Survival was also monitored daily until day 168. |
Dosage form | 30 mg/kg Gilteritinib from day 15 to day 70＿orally＿/p> |
Applications | Gilteritinib prolongs the survival of AML IBMT mice. |
| 产品描述 | Gilteritinib (ASP2215, Xospata) for relapsed and /or refractory AML (R/R AML). Gilteritinib is a small molecule dual inhibitor of FLT3/AXL with IC50s of 0.29 nM/0.73 nM[8]. When evaluated the antiproliferative activity of gilteritinib against MV4 11 and MOLM-13 cells, which endogenously express FLT3-ITD. After 5 days of treatment, gilteritinib inhibited the growth of MV4 11 and MOLM-13 cells with mean IC50 values of 0.92 nM (95% CI: 0.23 3.6 nM) and 2.9 nM[1]. gilteritinib has an inhibitory effect on ALK-TKI-resistant single mutants and I1171N compound mutants in vitro and in vivo. Gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer[3]. regardless of p53 status, treatment using gilteritinib induces PUMA in CRC cells via the NF-κB pathway after inhibition of AKT and activation of glycogen synthase kinase 3β (GSK-3β). PUMA was observed to be vital for apoptosis in CRC cells through treatment of gilteritinib[4]. Combination of Gilteritinib with ATO showed synergistic effects on inhibiting proliferation, increasing apoptosis and attenuating invasive ability in FLT3-ITD-mutated cells and reducing tumor growth in nude mice. Gilteritinib increased a 160KD form of FLT3 protein on the surface of cell membrane[5]. In the FLT3 signaling analyses, gilteritinib inhibited FLT3wt and FLT3-ITD to a similar degree in HEK293 and Ba/F3 cells, and similarly suppressed FLT3 downstream signaling molecules (including ERK1/2 and STAT5) in both the presence and absence of FL in MOLM-13 cells[6]. Combining gilteritinib with trametinib, a MEK1/2 inhibitor, is an effective means to target IgH-CRLF2-r ALL cells regardless of RAS mutational status[7]. Gilteritinib prolongs the survival of AML IBMT mice, MV4-11-luc tumor growth was significantly reduced during the first 2 weeks of treatment. Gilteritinib treatment significantly increased the survival of MV4-11 xenograft mice[1]. gilteritinib is already used to treat AML[2]. References: |
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