| CAS |
No.1239358-85-0 |
| 英文名称 |
Ilginatinib hydrochloride |
| 分子式 |
C21H21ClFN7 |
| 分子量 |
425.89 |
| 溶解性 |
Soluble in DMSO ≥3mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| 靶点 |
JAK |
| 通路 |
JAK/STAT Signaling |
| 背景说明 |
Ilginatinib hydrochloride 是一种高度有效的 JAK2 抑制剂。 |
| 生物活性 |
Ilginatinib hydrochloride (NS-018 hydrochloride) is a highly active and orally bioavailable JAK2 inhibitor， with an IC50 of 0.72 nM， 46-， 54-， and 31-fold selectivity for JAK2 over JAK1 (IC50， 33 nM)， JAK3 (IC50， 39 nM)， and Tyk2 (IC50， 22 nM).[1-2] |
| In Vitro |
Ilginatinib hydrochloride (NS-018 hydrochloride) is a highly active JAK2 inhibitor， with an IC50 of 0.72 nM， 46-， 54-， and 31-fold selectivity for JAK2 over JAK1 (IC50， 33 nM)， JAK3 (IC50， 39 nM)， and Tyk2 (IC50， 22 nM). Ilginatinib hydrochloride also inhibits Src-family kinases， especially SRC and FYN， and weakly inhibits ABL and FLT3 with 45- and 90-fold selectivity for JAK2， respectively. Ilginatinib hydrochloride shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene (expressing a constitutively activated JAK2) with IC50 of 11-120?nM， but has only minimal cytotoxicity against most other hematopoietic cell lines that have no constitutively activated JAK2[1]. Ilginatinib hydrochloride (0.5 μM) preferentially suppresses colony-forming unitgranulocyte/macrophage (CFU-GM) formation from myelodysplastic syndrome (MDS)-derived bone marrow mononuclear cells (BMMNCs). Ilginatinib hydrochloride (1 μM) suppresses the phosphorylation of STAT3 (the downstream kinase of JAK2) in CFU-GM-forming cells from MDS patients[2]. |
| In Vivo |
Ilginatinib hydrochloride (NS-018 hydrochloride) (12.5， 25， 50， 100 mg/kg， p.o.) potently prolongs the survival of mice and reduces splenomegaly in a mouse Ba/F3-JAK2V617F disease model[1].Ilginatinib hydrochloride (25， 50 mg/kg， p.o.) significantly reduces leukocytosis， hepatosplenomegaly and extramedullary hematopoiesis， improves nutritional status， and prolongs survival in JAK2V617F transgenic mice[1]. |
| 细胞实验 |
Bone marrow mononuclear cells (BMMNCs) from healthy volunteers and myelodysplastic syndrome (MDS) patients are incubated in MethoCult GF H4434 methylcellulose medium containing various hematopoietic cytokines at 1.0 × 105 cells/mL with or without Ilginatinib (NS-018) at 37°C in a humidified atmosphere of 5% CO2. Commercially available purified normal human CD34-positive (CD34+) BM cells are used as a control. Burst-forming unit-erythroid (BFU-E) and colonyforming unit-granulocyte/macrophage (CFU-GM) colonies are counted under an inverted microscope on day 14 of culture[2]. |
| 动物实验 |
Mice[1]Female BALB/c nude mice are placed in blanket cages in an environment maintained at 21-25°C and 45-65% relative humidity， with artificial illumination for 12?h and a ventilation frequency of at least 15?times/h. They are allowed free access to food pellets and tap water. Ba/F3-JAK2V617F cells (106 per mouse) are inoculated intravenously into 7-week-old mice. Administration of vehicle (0.5% methylcellulose) or Ilginatinib (NS-018) twice daily by oral gavage begins the day after cell inoculation. Survival is monitored daily， and moribund mice are humanely killed and their time of death is recorded for purposes of survival analysis. In a parallel study， all mice are humanely killed after 8 days of administration， and their spleens are removed and weighed[1]. |
| 数据来源文献 |
[1]. Nakaya Y， et al. Efficacy of NS-018， a potent and selective JAK2/Src inhibitor， in primary cells and mouse models of myeloproliferative neoplasms. Blood Cancer J. 2011 Jul;1(7):e29.
[2]. Kuroda J， et al. NS-018， a selective JAK2 inhibitor， preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients. Leuk Res. 2014 May;38(5):619-24. |
| 规格 |
1mg 5mg 10mg 25mg |
| 单位 |
瓶 |
中文
英语
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