CAS NO: | 1254053-84-3 |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
200mg | 电议 |
500mg | 电议 |
生物活性 | Gilteritinib (ASP2215) hemifumarate is a potent and ATP-competitiveFLT3/AXLinhibitor withIC50of 0.29 nM/0.73 nM, respectively. | ||||||||||||||||
IC50& Target | IC50: 0.29 nM (FLT3)[1] | ||||||||||||||||
体外研究 (In Vitro) | Of the 78 tyrosine kinases tested, Gilteritinib (ASP2215) inhibits FLT3, leukocyte tyrosine kinase (LTK), anaplastic lymphoma kinase (ALK), and AXL kinases by over 50% at 1 nM with an IC50value of 0.29 nM for FLT3, approximately 800-fold more potent than for c-KIT[1]. Gilteritinib inhibits 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 IC50s are 0.29 nM for FLT3 and 0.73 nM for AXL. Gilteritinib inhibits FLT3 at an IC50that is approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM). The antiproliferative activity of Gilteritinib is evaluated against MV4-11 and MOLM-13 cells, which endogenously express FLT3-ITD. After 5 days of treatment, Gilteritinib inhibits the growth of MV4-11 and MOLM-13 cells with mean IC50s of 0.92 nM (95% CI: 0.23-3.6 nM) and 2.9 nM (95% CI: 1.4-5.8 nM), respectively. Growth suppression of MV4-11 cells is accompanied by inhibition of FLT3 phosphorylation. Relative to vehicle control cells, phosphorylated FLT3 levels are 57%, 8%, and 1% after 2 h of treatment with 0.1 nM, 1 nM, and 10 nM Gilteritinib, respectively. In addition, doses as low as 0.1 nM or 1 nM result in the suppression of phosphorylated ERK, STAT5, and AKT, all of which are downstream targets of FLT3 activation. To investigate the effects of Gilteritinib on AXL inhibition, MV4-11 cells that expressed exogenous AXL are treated with Gilteritinib. At concentrations of 1 nM, 10 nM, and 100 nM for 4 h, Gilteritinib treatment decreases phosphorylated AXL levels by 38%, 29%, and 22%, respectively[2]. | ||||||||||||||||
体内研究 (In Vivo) | In MV4-11 xenografted-mice, the concentration of Gilteritinib (ASP2215) in tumors is more than 20-fold higher than that in plasma 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. Further, Gilteritinib decreases tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells[1]. | ||||||||||||||||
Clinical Trial | |||||||||||||||||
分子量 | 610.75 | ||||||||||||||||
性状 | Solid | ||||||||||||||||
Formula | C29H44N8O30.5C4H4O4 | ||||||||||||||||
CAS 号 | 1254053-84-3 | ||||||||||||||||
运输条件 | Room temperature in continental US; may vary elsewhere. | ||||||||||||||||
储存方式 | 4°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) | ||||||||||||||||
溶解性数据 | In Vitro: H2O : 2 mg/mL(3.27 mM;Need ultrasonic) Ethanol : 2 mg/mL(3.27 mM;ultrasonic and warming and adjust pH to 3 with 1M HCl and heat to 60℃) DMSO : 1.74 mg/mL(2.85 mM;Need ultrasonic and warming) 配制储备液
* 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 |